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5. The roles of homocysteinemia and methylmalonic acidemia in kidney injury in atypical hemolytic uremic syndrome caused by cobalamin C deficiency

Author

Wood, William D., Elmaghrabi, Ayah, Gotway, Garrett, and Wolf, Matthias T. F.

Subjects
Complications and side effects, Case studies, Risk factors, Health aspects, Methylmalonic acidemia -- Complications and side effects -- Case studies, Homocysteine -- Health aspects, Kidney diseases -- Risk factors -- Case studies, Vitamin B12 deficiency -- Complications and side effects -- Case studies
Abstract

Author(s): William D. Wood [sup.1] , Ayah Elmaghrabi [sup.1] , Garrett Gotway [sup.2] , Matthias T. F. Wolf [sup.1] Author Affiliations: (1) grid.267313.2, 0000 0000 9482 7121, Pediatric Nephrology, University [...], Background Cobalamin C (cblC), a vitamin B12 processing protein, plays a crucial role in metabolism for the conversion of homocysteine to methionine and methylmalonyl-CoA to succinyl-CoA. CblC deficiency, an inborn error of cobalamin processing, is a rare cause of atypical hemolytic-uremic syndrome (aHUS) and results in hyperhomocysteinemia and methylmalonic aciduria. Both substances are thought to contribute to thrombotic microangiopathy (TMA) in cblC deficiency patients. However, the roles of homocysteine and methylmalonic acid (MMA) in these patients remain unclear. We want to shed more light on the contributions of homocysteine and MMA levels as contributing factors for thrombotic microangiopathy (TMA)/aHUS by a follow-up of a cblC deficiency patient over 6 years. Case diagnosis A 27-day-old Hispanic female presented with abnormal C3-carnitine on her newborn screen, poor feeding, decreased activity, and oligouria. She was diagnosed with cblC deficiency after laboratory results revealed elevated serum homocysteine, and serum MMA along with genetic testing showing a homozygous pathogenic frameshift variant in MMACHC. The patient developed aHUS and acute kidney injury (AKI), which resolved after appropriate therapy. Over 6 years, she continued to have normal kidney function with no thrombocytopenia despite persistently elevated homocysteine and MMA levels. Conclusion We question the roles of homocysteine and MMA as causative of aHUS/TMA in cblC deficiency as they remained elevated during follow-up but did not result in aHUS/TMA or AKI. Hyperhomocysteinemia and/or MMA caused by other metabolic diseases do not result in aHUS/TMA or AKI. This suggests that other nephrotoxic factors may trigger aHUS/TMA in cblC patients.

Published
2022
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6. Autosomal dominant tubulointerstitial kidney disease: more than just HNF1[beta]

Author

Bleyer, Anthony J., Wolf, Matthias T., Kidd, Kendrah O., Zivna, Martina, and Kmoch, Stanislav

Subjects
Diagnosis, Complications and side effects, Development and progression, Genetic aspects, Risk factors, Rare diseases -- Complications and side effects -- Diagnosis -- Genetic aspects, Chronic kidney failure -- Risk factors -- Development and progression
Abstract

Author(s): Anthony J. Bleyer [sup.1] [sup.2] , Matthias T. Wolf [sup.3] , Kendrah O. Kidd [sup.1] [sup.2] , Martina Zivna [sup.2] , Stanislav Kmoch [sup.1] [sup.2] Author Affiliations: (1) grid.241167.7, [...], Autosomal dominant tubulointerstitial kidney disease (ADTKD) refers to a group of disorders with a bland urinary sediment, slowly progressive chronic kidney disease (CKD), and autosomal dominant inheritance. Due to advances in genetic diagnosis, ADTKD is becoming increasingly recognized as a cause of CKD in both children and adults. ADTKD-REN presents in childhood with mild hypotension, CKD, hyperkalemia, acidosis, and anemia. ADTKD-UMOD is associated with gout and CKD that may present in adolescence and slowly progresses to kidney failure. HNF1[beta] mutations often present in childhood with anatomic abnormalities such as multicystic or dysplastic kidneys, as well as CKD and a number of other extra-kidney manifestations. ADTKD-MUC1 is less common in childhood, and progressive CKD is its sole clinical manifestation, usually beginning in the late teenage years. This review describes the pathophysiology, genetics, clinical characteristics, diagnosis, and treatment of the different forms of ADTKD, with an emphasis on diagnosis. We also present data on kidney function in children with ADTKD from the Wake Forest Rare Inherited Kidney Disease Registry.

Published
2022
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7. A rare case of hyporeninemic hypertension: Answers

Author

Mashmoushi, Ahmad, Choudhary, Abha, Thomas, Christie P., and Wolf, Matthias T. F.

Subjects
Diagnosis, Research, Causes of, Pediatric research, Hypertension -- Diagnosis -- Causes of, Plasma renin activity -- Research, Genetic disorders -- Diagnosis, Kidney function tests -- Research
Abstract

Author(s): Ahmad Mashmoushi [sup.1] , Abha Choudhary [sup.2] , Christie P. Thomas [sup.3] , Matthias T. F. Wolf [sup.1] [sup.4] Author Affiliations: (1) grid.267313.2, 0000 0000 9482 7121, Pediatric Nephrology, [...]

Published
2020
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9. Ghrelin enhances tubular magnesium absorption in the kidney.

Author

Mingzhu Nie, Jing Zhang, Bal, Manjot, Duran, Claudia, Sung Wan An, Zigman, Jeffrey M., Baum, Michel, Hiremath, Chitkale, Marciano, Denise K., and Wolf, Matthias T. F.

Subjects
GHRELIN receptors, GHRELIN, MAGNESIUM, CA 19-9 test, SERUM, LOW-calorie diet, CALCIUM channels, GASTRIC bypass
Abstract

Osteoporosis after bariatric surgery is an increasing health concern as the rate of bariatric surgery has risen. In animal studies mimicking bariatric procedures, bone disease, together with decreased serum levels of Ca2+, Mg2+ and the gastric hormone Ghrelin were described. Ghrelin regulates metabolism by binding to and activating the growth hormone secretagogue receptor (GHSR) which is also expressed in the kidney. As calcium and magnesium are key components of bone, we tested the hypothesis that Ghrelin-deficiency contributes to osteoporosis via reduced upregulation of the renal calcium channel TRPV5 and the heteromeric magnesium channel TRPM6/7. We expressed GHSR with TRPV5 or TRPM6/7 channel in HEK293 cells and treated them with purified Ghrelin. Whole-cell current density was analyzed by patch-clamp recording. Nephron-specific gene expression was performed by tubular microdissection followed by qPCR in wild-type (WT) mice, and immunofluorescent imaging of GHSR-eGFP mice. Tubular magnesium homeostasis was analyzed in GHSR-null and WT mice at baseline and after caloric restriction. After Ghrelin exposure, whole-cell current density did not change for TRPV5 but increased for TRPM6/7 in a dose-dependent fashion. Applying the Ghrelin-mimetic (D-Trp7, Ala8,D-Phe10)-α-MSH (6-11) amide without and with the GHSR antagonist (D-Lys3)-GHRP6, we confirmed the stimulatory role of Ghrelin towards TRPM6/7. As GHSR initiates downstream signaling via protein kinase A (PKA), we found that the PKA inhibitor H89 abrogated TRPM6/7 stimulation by Ghrelin. Similarly, transfected Gαs, but not the Gαs mutant Q227L, nor Gαi2, Gαq, or Gα13 upregulated TRPM6/7 current density. In microdissected TALs and DCTs similar levels of GHSR mRNA were detected. In contrast, TRPM6 mRNA was expressed in the DCT and also detected in the TAL at 25% expression compared to DCT. Immunofluorescent studies using reporter GHSR-eGFP mice showed a strong eGFP signal in the TAL but surprisingly displayed no eGFP signal in the DCT. In 3-, 6-, and 9-month-old GHSR-null and WT mice, baseline serum magnesium was not significantly different, but 24-h urinary magnesium excretion was elevated in 9-month-old GHSR-null mice. In calorically restricted GHSR-null mice, we detected excess urinary magnesium excretion and reduced serum magnesium levels compared to WT mice. The kidneys from calorically restricted WT mice showed upregulated gene expression of magnesiotropic genes Hnf1b, Cldn-16, Cldn-19, Fxyd-2b, and Parvalbumin compared to GHSR-null mice. Our in vitro studies show that Ghrelin stimulates TRPM6/7 via GHSR and Gαs-PKA signaling. The murine studies are consistent with Ghrelin-GHSR signaling inducing reduced urinary magnesium excretion, particularly in calorically restricted mice when Ghrelin levels are elevated. This effect may be mediated by Ghrelin-upregulation of TRPM6 in the TAL and/or upregulation of other magnesiotropic genes. We postulate that rising Ghrelin levels with hunger contribute to increased renal Mg2+ reabsorption to compensate for lack of enteral Mg2+ uptake. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Renal Tubular Acidosis in Children

Author

Quigley, Raymond, Wolf, Matthias T. F., Avner, Ellis D., editor, Harmon, William E., editor, Niaudet, Patrick, editor, Yoshikawa, Norishige, editor, Emma, Francesco, editor, and Goldstein, Stuart L., editor

Published
2016
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13. Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly

Author

Braun, Daniela A, Rao, Jia, Mollet, Geraldine, Schapiro, David, Daugeron, Marie-Claire, Tan, Weizhen, Gribouval, Olivier, Boyer, Olivia, Revy, Patrick, Jobst-Schwan, Tilman, Schmidt, Johanna Magdalena, Lawson, Jennifer A, Schanze, Denny, Ashraf, Shazia, Ullmann, Jeremy F P, Hoogstraten, Charlotte A, Boddaert, Nathalie, Collinet, Bruno, Martin, Gaëlle, Liger, Dominique, Lovric, Svjetlana, Furlano, Monica, Guerrera, I Chiara, Sanchez-Ferras, Oraly, Hu, Jennifer F, Boschat, Anne-Claire, Sanquer, Sylvia, Menten, Björn, Vergult, Sarah, De Rocker, Nina, Airik, Merlin, Hermle, Tobias, Shril, Shirlee, Widmeier, Eugen, Gee, Heon Yung, Choi, Won-Il, Sadowski, Carolin E, Pabst, Werner L, Warejko, Jillian K, Daga, Ankana, Basta, Tamara, Matejas, Verena, Scharmann, Karin, Kienast, Sandra D, Behnam, Babak, Beeson, Brendan, Begtrup, Amber, Bruce, Malcolm, Ch'ng, Gaik-Siew, Lin, Shuan-Pei, Chang, Jui-Hsing, Chen, Chao-Huei, Cho, Megan T, Gaffney, Patrick M, Gipson, Patrick E, Hsu, Chyong-Hsin, Kari, Jameela A, Ke, Yu-Yuan, Kiraly-Borri, Cathy, Lai, Wai-ming, Lemyre, Emmanuelle, Littlejohn, Rebecca Okashah, Masri, Amira, Moghtaderi, Mastaneh, Nakamura, Kazuyuki, Ozaltin, Fatih, Praet, Marleen, Prasad, Chitra, Prytula, Agnieszka, Roeder, Elizabeth R, Rump, Patrick, Schnur, Rhonda E, Shiihara, Takashi, Sinha, Manish D, Soliman, Neveen A, Soulami, Kenza, Sweetser, David A, Tsai, Wen-Hui, Tsai, Jeng-Daw, Topaloglu, Rezan, Vester, Udo, Viskochil, David H, Vatanavicharn, Nithiwat, Waxler, Jessica L, Wierenga, Klaas J, Wolf, Matthias T F, Wong, Sik-Nin, Leidel, Sebastian A, Truglio, Gessica, Dedon, Peter C, Poduri, Annapurna, Mane, Shrikant, Lifton, Richard P, Bouchard, Maxime, Kannu, Peter, Chitayat, David, Magen, Daniella, Callewaert, Bert, van Tilbeurgh, Herman, Zenker, Martin, Antignac, Corinne, and Hildebrandt, Friedhelm

Published
2017
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14. Insulin receptor substrate 4 deficiency mediates the insulin effect on the epithelial magnesium channel TRPM6 and causes hypomagnesemia

Author

Zhang, Jing, primary, An, Sung Wan, additional, Neelam, Sudha, additional, Bhatta, Anuja, additional, Nie, Mingzhu, additional, Duran, Claudia, additional, Bal, Manjot, additional, Latta, Femke, additional, Hou, Jianghui, additional, Otto, Joseph J., additional, Kozlitina, Julia, additional, Lemoff, Andrew, additional, Hoenderop, Joost, additional, Baum, Michel, additional, and Wolf, Matthias T, additional

Published
2022
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17. Contributors

Author

Abbasi, Soraya, primary, Abbey, James, additional, Adzick, N. Scott, additional, Ahn, Sun-Young, additional, Albertine, Kurt H., additional, Allegaert, Karel, additional, Alper, Seth L., additional, Altit, Gabriel, additional, Altschuler, Steven M., additional, Alvaro, Ruben E., additional, Amorosa, Jennifer M.H., additional, Anbuhl, Kelsey L., additional, Andersen, Claus Yding, additional, Anderson, Richard A., additional, Askenazi, David J., additional, Auten, Richard Lambert, additional, Autmizguine, Julie, additional, Azhibekov, Timur, additional, Back, Stephen A., additional, Badaut, Jérôme, additional, Baker, Peter Russell, additional, Ballard, Philip L., additional, Bancalari, Eduardo H., additional, Barichello, Tatiana, additional, Battaglia, Frederick, additional, Baum, Michel, additional, Beggs, Simon, additional, Bell, Edward F., additional, Benchimol, Corinne, additional, Benders, Manon J.N.L., additional, Bennet, Laura, additional, Bennett, Phillip R., additional, Berger, Melvin, additional, Bernhard, Wolfgang, additional, Bertram, John F., additional, Bhosle, Vikrant K., additional, Bhutani, Vinod K., additional, Black, M. Jane, additional, Bliss, Joseph M., additional, Bolender, David L., additional, Brandenburg, Joline E., additional, Broussard, Delma L., additional, Brown, Laura Davidson, additional, Burrin, Douglas G., additional, Cannon, Barbara, additional, Caplan, Michael, additional, Carlson, Susan E., additional, Carlton, David P., additional, Caruana, Georgina, additional, Cashore, William J., additional, Chaemsaithong, Piya, additional, Chaiyasit, Noppadol, additional, Charlton, Jennifer R., additional, Cheatham, Carol L., additional, Chemtob, Sylvain, additional, Chen, Yi-Yung, additional, Chevalier, Robert L., additional, Chheda, Sadhana, additional, Childs, Andrew J., additional, Christensen, Robert D., additional, Chu, Alison, additional, Chu, David H., additional, Cilio, Maria Roberta, additional, Clark, David A., additional, Cleary-Goldman, Jane, additional, Clemente, Ethel G., additional, Clements, John A., additional, Clyman, Ronald I., additional, Cohen, Susan S., additional, Colombo, John, additional, Cowett, Richard M., additional, Crawford, Peter A., additional, Crowe, James E., additional, Cullen-McEwen, Luise A., additional, Cutfield, Wayne S., additional, D'Alton, Mary E., additional, Danzer, Enrico, additional, Delacourt, Christophe, additional, Devaskar, Sherin U., additional, Diacovo, Thomas G., additional, Docheva, Nikolina, additional, Dormans, John P., additional, Dysart, Kevin, additional, El-Khuffash, Afif, additional, Ellis, Peter James, additional, Empey, Kerry McGarr, additional, Ercal, Baris, additional, Erdős, Melinda, additional, Erickson, Robert P., additional, Fahim, Mohamed A., additional, Faksh, Arij, additional, Frank, Hans-Georg, additional, Friedlich, Philippe S., additional, Friedman, Jed, additional, Gao, Yuansheng, additional, Garland, Marianne, additional, Geddes, Donna, additional, Georgieff, Michael K., additional, Gien, Jason, additional, Giussani, Dino A., additional, Goldman, Armond S., additional, González, Efrén, additional, Good, Misty, additional, Grant, Denis M., additional, Green, Lucy R., additional, Grigoriou, Emmanouil, additional, Grimberg, Adda, additional, Gross, Ian, additional, Grunau, Ruth E., additional, Guignard, Jean-Pierre, additional, Gunn, Alistair Jan, additional, Gurtunca, Nursen, additional, Hadchouel, Alice, additional, Haddad, Gabriel G., additional, Hagberg, Henrik, additional, Hale, Thomas, additional, Hambidge, K. Michael, additional, Hammerman, Cathy, additional, Hansen, Thor Willy Ruud, additional, Hanson, Mark A., additional, Harding, Richard, additional, Harris, Mary Catherine, additional, Hartmann, Peter, additional, Hassiotou, Foteini, additional, Haugen, Guttorm, additional, Hawkes, Colin P., additional, Hay, William W., additional, Hayward, Christina E., additional, Heine, Vivi M., additional, Hellström, Ann, additional, Helmrath, Michael A., additional, Hendricks-Muñoz, Karen D., additional, Herrera, Emilio, additional, Hiatt, Michael J., additional, Hoath, Steven B., additional, Hooper, Stuart B., additional, Huang, Stephen A., additional, Iacobellli, Silvia, additional, Inder, Terrie E., additional, Iruela-Arispe, M. Luisa, additional, Jadcherla, Sudarshan R., additional, Jain, Deepak, additional, Jansson, Thomas, additional, Jefferies, John Lynn, additional, Jetton, Jennifer G., additional, Jobe, Alan H., additional, Johnson, Lois H., additional, Johnston, Richard B., additional, Jones, Rebecca Lee, additional, Jose, Pedro A., additional, Kalhan, Satish C., additional, Kallapur, Suhas G., additional, Kaplan, Michael, additional, Kaplan, Stanley, additional, Karpen, Heidi Eigenrauch, additional, Karpen, Saul J., additional, Karumanchi, S. Ananth, additional, Kaskel, Frederick J., additional, Katheria, Anup C., additional, Katz, Lorraine E. Levitt, additional, Keeney, Susan E., additional, Kern, Steven E., additional, Khanjani, Shirin, additional, Kilpatrick, Laurie E., additional, Kim, Chang-Ryul, additional, Kinsella, John P., additional, Kiserud, Torvid, additional, Koenig, Joyce M., additional, Kollmann, Tobias R., additional, Kolls, Jay K., additional, Krebs, Nancy F., additional, Kulik, Thomas J., additional, Kutikov, Jessica Katz, additional, Lakshminrusimha, Satyan, additional, Lamola, Angelo A., additional, Lasunción, Miguel Angel, additional, Lavoie, Pascal M., additional, LeBien, Tucker W., additional, Lee, Mary M., additional, Lee, Matthew K., additional, Lee, Yvonne K., additional, Leibel, Sandra, additional, Levine, Fred, additional, Levy, Ofer, additional, Liu, Yang, additional, Lobritto, Steven, additional, Loomis, Cynthia A., additional, Lopez, Colleen A., additional, MacIntyre, David A., additional, Mahe, Maxime M., additional, Maheshwari, Akhil, additional, Mankouski, Anastasiya, additional, Mantilla, Carlos B., additional, Marchant, Arnaud, additional, Margolis, Kara Gross, additional, Mariscalco, M. Michele, additional, Maródi, László, additional, Maršál, Karel, additional, Martin, Richard J., additional, Matsell, Douglas G., additional, Matthews, Dwight E., additional, McArdle, Harry J., additional, McManaman, James L., additional, McNamara, Patrick J., additional, McQuillen, Patrick S., additional, McQuinn, Tim C., additional, Mercer, Judith S., additional, Meschia, Giacomo, additional, Miller, Steven P., additional, Minoo, Parviz, additional, Monagle, Paul, additional, Mortola, Jacopo P., additional, Muglia, Louis J., additional, Munshi, Upender K., additional, Namgung, Ran, additional, Narasimhan, Sumana, additional, Nedergaard, Jan, additional, Neu, Josef, additional, Nigam, Sanjay K., additional, Nogee, Lawrence M., additional, Noori, Shahab, additional, O'Brien, Barbara M., additional, Ohls, Robin K., additional, Ortega-Senovilla, Henar, additional, O'Sullivan, Justin M., additional, Owusu, Sarah A., additional, Pal, Abhijeet, additional, Panitch, Howard B., additional, Penn, Anna A., additional, Penn, Raymond B., additional, Pernia, Cameron, additional, Philipps, Anthony F., additional, Picoraro, Joseph A., additional, Pisani, Francesco, additional, Pleasure, David, additional, Pleasure, Jeanette R., additional, Pleasure, Samuel J., additional, Pomeroy, Scott L., additional, Post, Martin, additional, Prakash, Y.S., additional, Prozialeck, Joshua D., additional, Pysher, Theodore J., additional, Quigley, Raymond, additional, Rabinovitch, Marlene, additional, Raffay, Thomas M., additional, Raj, J. Usha, additional, Ramsey, Haley, additional, Rana, Sarosh, additional, Randis, Tara Marie, additional, Ranger, Manon, additional, Ratner, Adam J., additional, Regnault, Timothy R.H., additional, Rigatto, Henrique, additional, Rintoul, Natalie E., additional, Romero, Roberto, additional, Rose, James C., additional, Rosenfeld, Charles R., additional, Ross, A. Catharine, additional, Rozycki, Henry J., additional, Ryan, Thomas D., additional, Sahni, Rakesh, additional, Sajti, Eniko, additional, Sarnat, Harvey B., additional, Satlin, Lisa M., additional, Saugstad, Ola Didrik, additional, Schierding, William, additional, Schmalstieg, Frank C., additional, Schwartz, George J., additional, Schwartz, Jeffrey, additional, Segar, Jeffrey L., additional, Selewski, David T., additional, Seri, Istvan, additional, Shaffer, Thomas H., additional, Shah, Kara N., additional, Shearer, Martin J., additional, Shojaie, Sharareh, additional, Shroyer, Noah F., additional, Sibley, Colin P., additional, Sieck, Gary C., additional, Simmons, Rebecca A., additional, Sivieri, Emidio M., additional, Smith, Francine G., additional, Smith, Lois E.H., additional, Smyth, Ian M., additional, Snarr, Brian S., additional, Snyder, Evan Y., additional, Sola-Visner, Martha, additional, Solhaug, Michael J., additional, Sperling, Mark A., additional, Srinivasan, Lakshmi, additional, Stahl, Andreas, additional, Stanley, Charles A., additional, Steinhorn, Robin H., additional, Stonestreet, Barbara S., additional, Strasburger, Janette F., additional, Styne, Dennis M., additional, Sussel, Lori, additional, Tam, Emily W.Y., additional, Tan, Libo, additional, Thornton, Claire, additional, Tollin, Daniel J., additional, Tóth, Beáta, additional, Towbin, Jeffrey A., additional, Trocle, Ashley, additional, Truog, William E., additional, Tsang, Reginald C., additional, Uhler, Kristin M., additional, Van Den Anker, John N., additional, van Goudoever, Johannes (Hans) B., additional, Vannucci, Susan J., additional, Vickers, Mark H., additional, Virgintino, Daniela, additional, Volpe, Joseph J., additional, Vora, Neeta L., additional, Vyas, Neha V., additional, Wacker-Gussmann, Annette, additional, Wallace, Megan J., additional, Walsh, Brian H., additional, Wang, Alice M., additional, Warburton, David, additional, Ward, Robert M., additional, Watterberg, Kristi L., additional, Werner, Lynne A., additional, Wershil, Barry K., additional, Wert, Susan E., additional, Wessels, Andy, additional, Whitsett, Jeffrey A., additional, Wise, Michael, additional, Wolf, Matthias T., additional, Wolfson, Marla R., additional, Wong, Hector R., additional, Wynn, James L., additional, Yeo, Lami, additional, Yip, Stephen, additional, Yoder, Bradley A, additional, Yoder, Mervin C., additional, Yoshimoto, Momoko, additional, Yuskaitis, Christopher J., additional, Zhou, Dan, additional, and Zovein, Ann, additional

Published
2017
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20. Gentamicin induces calciuresis by blocking TRPV5

Author

Megen, Wouter H., primary, Beggs, Megan R., additional, An, Sung‐Wan, additional, Ferreira, Patrícia G., additional, Lee, Justin J., additional, Wolf, Matthias T., additional, Alexander, R. T., additional, and Dimke, Henrik, additional

Published
2022
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31. A gene mutated in nephronophthisis and retinitis pigmentosa encodes a novel protein, nephroretinin, conserved in evolution

Author

Otto, Edgar, Hoefele, Julia, Ruf, Rainer, Mueller, Adelheid M., Hiller, Karl S., Wolf, Matthias T. F., Schuermann, Maria J., Becker, Achim, Birkenhager, Ralf, Sudbrak, Ralf, Hennies, Hans C.Nurnberg, Peter, and Hildebrandt, Friedhelm

Subjects
Cloning -- Research, Gene mutations -- Physiological aspects, Genetic disorders -- Research, Haplotypes -- Analysis, Kidney diseases -- Genetic aspects, Biological sciences
Published
2002

32. Mutation analysis of 18 nephronophthisis associated ciliopathy disease genes using a DNA pooling and next generation sequencing strategy

Author

Otto, Edgar A, Ramaswami, Gokul, Janssen, Sabine, Chaki, Moumita, Allen, Susan J, Zhou, Weibin, Airik, Rannar, Hurd, Toby W, Ghosh, Amiya K, Wolf, Matthias T, Hoppe, Bernd, Neuhaus, Thomas J, Bockenhauer, Detlef, Milford, David V, Soliman, Neveen A, Antignac, Corinne, Saunier, Sophie, Johnson, Colin A, and Hildebrandt, Friedhelm

Published
2011
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35. An international cohort study of autosomal dominant tubulointerstitial kidney disease due to REN mutations identifies distinct clinical subtypes

Author

Zivna, Martina, Kidd, Kendrah, Zaidan, Mohamad, Vyletal, Petr, Baresova, Veronika, Hodanova, Katerina, Sovova, Jana, Hartmannova, Hana, Votruba, Miroslav, Treslova, Helena, Jedlickova, Ivana, Sikora, Jakub, Hulkova, Helena, Robins, Victoria, Hnizda, Ales, Zivny, Jan, Papagregoriou, Gregory, Mesnard, Laurent, Beck, Bodo B., Wenzel, Andrea, Tory, Kalman, Haeeffner, Karsten, Wolf, Matthias T. F., Bleyer, Michael E., Sayer, John A., Ong, Albert C. M., Balogh, Lidia, Jakubowska, Anna, Laszkiewicz, Agnieszka, Clissold, Rhian, Shaw-Smith, Charles, Munshi, Raj, Haws, Robert M., Izzi, Claudia, Capelli, Irene, Santostefano, Marisa, Graziano, Claudio, Scolari, Francesco, Sussman, Amy, Trachtman, Howard, Decramer, Stephane, Matignon, Marie, Grimbert, Philippe, Shoemaker, Lawrence R., Stavrou, Christoforos, Abdelwahed, Mayssa, Belghith, Neila, Sinclair, Matthew, Claes, Kathleen, Kopel, Tal, Moe, Sharon, Deltas, Constantinos, Knebelmann, Bertrand, Rampoldi, Luca, Kmoch, Stanislav, Bleyer, Anthony J., Zivna, Martina, Kidd, Kendrah, Zaidan, Mohamad, Vyletal, Petr, Baresova, Veronika, Hodanova, Katerina, Sovova, Jana, Hartmannova, Hana, Votruba, Miroslav, Treslova, Helena, Jedlickova, Ivana, Sikora, Jakub, Hulkova, Helena, Robins, Victoria, Hnizda, Ales, Zivny, Jan, Papagregoriou, Gregory, Mesnard, Laurent, Beck, Bodo B., Wenzel, Andrea, Tory, Kalman, Haeeffner, Karsten, Wolf, Matthias T. F., Bleyer, Michael E., Sayer, John A., Ong, Albert C. M., Balogh, Lidia, Jakubowska, Anna, Laszkiewicz, Agnieszka, Clissold, Rhian, Shaw-Smith, Charles, Munshi, Raj, Haws, Robert M., Izzi, Claudia, Capelli, Irene, Santostefano, Marisa, Graziano, Claudio, Scolari, Francesco, Sussman, Amy, Trachtman, Howard, Decramer, Stephane, Matignon, Marie, Grimbert, Philippe, Shoemaker, Lawrence R., Stavrou, Christoforos, Abdelwahed, Mayssa, Belghith, Neila, Sinclair, Matthew, Claes, Kathleen, Kopel, Tal, Moe, Sharon, Deltas, Constantinos, Knebelmann, Bertrand, Rampoldi, Luca, Kmoch, Stanislav, and Bleyer, Anthony J.

Abstract

There have been few clinical or scientific reports of autosomal dominant tubulointerstitial kidney disease due to REN mutations (ADTKD-REN), limiting characterization. To further study this, we formed an international cohort characterizing 111 individuals from 30 families with both clinical and laboratory findings. Sixty-nine individuals had a REN mutation in the signal peptide region (signal group), 27 in the prosegment (prosegment group), and 15 in the mature renin peptide (mature group). Signal group patients were most severely affected, presenting at a mean age of 19.7 years, with the prosegment group presenting at 22.4 years, and the mature group at 37 years. Anemia was present in childhood in 91% in the signal group, 69% prosegment, and none of the mature group. REN signal peptide mutations reduced hydrophobicity of the signal peptide, which is necessary for recognition and translocation across the endoplasmic reticulum, leading to aberrant delivery of preprorenin into the cytoplasm. REN mutations in the prosegment led to deposition of prorenin and renin in the endoplasmic reticulum-Golgi intermediate compartment and decreased prorenin secretion. Mutations in mature renin led to deposition of the mutant prorenin in the endoplasmic reticulum, similar to patients with ADTKD-UMOD, with a rate of progression to end stage kidney disease (63.6 years) that was significantly slower vs. the signal (53.1 years) and prosegment groups (50.8 years) (significant hazard ratio 0.367). Thus, clinical and laboratory studies revealed subtypes of ADTKD-REN that are pathophysiologically, diagnostically, and clinically distinct.

Published
2020

38. Contributors

Author

Abbasi, Soraya, Afshar, Yalda, Ahn, Sun-Young, Albertine, Kurt H., Allegaert, Karel, Alper, Seth L., Altit, Gabriel, Alvaro, Ruben E., Alvira, Cristina M., Maia Amorim, Natália Carlos, Anbuhl, Kelsey L., Andersen, Claus Yding, Anderson, Richard A., Andrews, Katrina A., Askenazi, David J., Fernandes Assunção, Débora Gabriela, Auten, Richard Lambert, Jr., Autmizguine, Julie, Azhibekov, Timur, Back, Stephen A., Bahr, Timothy M., Baker, Peter Russell, II, Bancalari, Eduardo H., Barichello, Tatiana, Battaglia, Frederick C., Bauer, Andrew J., Baum, Michel, Bavis, Ryan W., Beardsall, Kathryn, Beggs, Simon, Benchimol, Corinne, Benders, Manon J.N.L., Bennet, Laura, Bennett, Phillip R., Berger, Melvin, Bernhard, Wolfgang, Bertram, John F., Bhombal, Shazia, Bhutani, Vinod K., Black, Mary Jane, Bliss, Joseph M., Bolender, David L., Bowdin, Sarah C., Boyd, Scott D., Brandenburg, Joline E., Brown, Laura D., Burrin, Douglas G., Cannon, Barbara, Caplan, Michael, Carlson, Susan E., Carlton, David P., Chaemsaithong, Piya, Chang, Jill, Charlton, Jennifer R., Chemtob, Sylvain, Chheda, Sadhana, Childs, Andrew J., Chu, David H., Chung, Wendy K., Cilio, Maria Roberta, Clark, David A., Clarke, Paul, Cleal, Jane K., Clemente, Ethel G., Clements, John A., Clyman, Ronald I., Cohen, Jennifer L., Cohen, Susan S., Collins, Amélie, Collodel, Allan, Colombo, John, Combes, Alexander N., Copp, Andrew J., Cotten, C. Michael, Crawford, Peter A., Crowe, James E., Jr., Crowther, C.A., Cullen-McEwen, Luise A., Cutfield, Wayne S., Cyr-Depauw, Chanèle, Danielly da S. Ribeiro, Karla, Dauby, Nicolas, Davenport, Patricia, Davidson, Joanne O., Cruz, Diomel de la, Gomes de Oliveira, Priscila, de Vrijer, Barbra, Del Colle, Andrew, Delacourt, Christophe, Diacovo, Thomas G., Disdier, Clémence, Dormans, John P., Duhamel, François, Duong, Minh Dien, Dysart, Kevin, Eichenwald, Eric C., El-Khuffash, Afif F., Ivor Ellis, Peter James, Empey, Kerry M., Ercal, Baris, Erdős, Melinda, Errede, Mariella, Feldman, Brian J., Fidanza, Mario, Fogarty, Matthew J., Friedlich, Philippe S., Fujiwara, Ryoichi, Gallo, Vittorio, Ganguly, Abhrajit, Gao, Yuansheng, Garland, Marianne, Geddes, Donna, Dip (Sci), Post Grad, Georgieff, Michael K., Gien, Jason, Giussani, Dino A., Goldman, Armond S., Gomez-Lopez, Nardhy, Good, Misty, Good, Pamela I., Gordon, Scott M., Green, Lucy R., Greene, Nicholas D.E., Gridneva, Zoya, Grigoriou, Emmanouil, Grimberg, Adda, Grunau, Ruth E., Guignard, Jean-Pierre, Gunn, Alistair J., Gurtunca, Nursen, Gustafson, Kathleen M., Hadchouel, Alice, Haddad, Gabriel G., Hale, Thomas W., Hambidge, K. Michael, Hammerman, Cathy, Ruud Hansen, Thor Willy, Hanson, Mark A., Harbeson, Danny, Harding, J.E., Harding, Richard, Harris, Mary Catherine, Hartmann, Peter, Hartnett, M. Elizabeth, Hasbun, Rodrigo, Haugen, Guttorm, Hawkes, Colin P., Hay, William W., Jr., Heine, Vivi M., Helmrath, Michael A., Hendricks-Muñoz, Karen D., Herrera, Emilio, Hiatt, Michael J., Hooper, Stuart B., Hooven, Thomas A., Iacobelli, Silvia, Inder, Terrie E., Iruela-Arispe, M. Luisa, Jadcherla, Sudarshan Rao, Jain, Deepak, Jetton, Jennifer G., Jobe, Alan H., Jones, Helen, Jose, Pedro A., Jung, Eunjung, Kallapur, Suhas G., Kaplan, Michael, Karumanchi, S. Ananth, Kaskel, Frederick J., Levitt Katz, Lorraine E., Kavus, Haluk, Keeney, Susan E., Kern, Steven E., Khanjani, Shirin, Khlevner, Julie, Kilpatrick, Laurie E., Kim, Chang-Ryul, Kingma, Paul S., Kinsella, John P., Kiserud, Torvid, Koenig, Joyce M., Kohli, Rohit, Kollmann, Tobias R., Kolls, Jay K., Konecny, Christina M., Kratimenos, Panagiotis, Krebs, Nancy F., Krutsch, Kaytlin, Kuhn-Riordon, Kara, Kulik, Thomas J., Kumar, T. Rajendra, Kutikov, Jessica Katz, Lakshminrusimha, Satyan, Lasunción, Miguel Angel, Lavoie, Pascal M., Lawrence, Shelley M., Lee, Mark K., Lee, Mary M., Lee, Yvonne K., Leibel, Sandra L., Levy, Ofer, Levy, Philip T., Lewis, Rohan M., Li, Changgong, Lin, Fangming, Lobritto, Steven, Loomis, Cynthia A., MacFarlane, Peter M., MacIntyre, David A., Mahe, Maxime M., Mamsen, Linn Salto, Mankouski, Anastasiya, Mantilla, Carlos B., Marchant, Arnaud, Margolis, Kara Gross, Maródi, László, Maršál, Karel, Martin, Richard J., Martin Carli, Jayne F., Martinez, Hugo R., Matsell, Douglas G., Matthews, Dwight E., McArdle, Harry J., McKinlay, C.J.D., McManaman, James L., McNamara, Patrick J., Meschia, Giacomo, Mestan, Karen, Miller, Steven P., Minoo, Parviz, Mir, Imran N., Mitchell, Lisa J., Mižíková, Ivana, Mizuno, Tomoyuki, Momper, Jeremiah D., Monagle, Paul, Monks, Jenifer, Mortola, Jacopo P., Muglia, Louis J., Munshi, Upender K., Narasimhan, Sumana, Narendran, Vivek, Nedergaard, Jan, Nelin, Leif D., Neu, Josef, Nielsen, Sandra C.A., Nigam, Sanjay K., Nizet, Victor, Nogee, Lawrence M., Noori, Shahab, Norris, Andrew W., O’Brien, Barbara M., O’Brien, Lori L., O’Callaghan, Karen M., Ogilvy-Stuart, Amanda, Ohls, Robin K., Ortega-Senovilla, Henar, O’Sullivan, Justin M., Panitch, Howard B., Penn, Anna A., Penn, Raymond B., Petroff, Margaret G., Philipps, Anthony F., Pisani, Francesco, Pleasure, David, Pomeroy, Scott L., Post, Martin, Prakash, Y.S., Prozialeck, Joshua D., Pysher, Theodore J., Quigley, Raymond, Rabinovitch, Marlene, Raffay, Thomas M., Raj, J. Usha, Ramsey, Laura B., Rana, Sarosh, Randis, Tara M., Ranger, Manon, Regnault, Timothy R.H., Rios, Danielle R., Romero, Roberto, Rosenfeld, Charles R., Ross, A. Catharine, Roth, Daniel E., Rozycki, Henry J., Ryan, Thomas D., Sahni, Rakesh, Sarnat, Harvey B., Satlin, Lisa M., Scafidi, Joseph, Schellpfeffer, Michael A., Schierding, William, Schwartz, George J., Segar, Jeffrey L., Selewski, David T., Seri, Istvan, Shaffer, Thomas H., Shearer, Martin J., Shroyer, Noah F., Sieck, Gary C., Simmons, Rebecca A., Singh, Neel Kamal, Sivieri, Emidio, Smith, Laura, Smyth, Ian M., Sola-Visner, Martha C., Solhaug, Michael J., Sperandio, Markus, Sperling, Mark A., Srinivasan, Lakshmi, Stanescu, Diana E., Stanley, Charles A., Steinhorn, Robin H., Stinson, Lisa, Stonestreet, Barbara S., Strasburger, Janette F., Styne, Dennis M., Sun, Xin, Sussel, Lori, Tam, Emily W.Y., Tan, Libo, te Pas, Arjan B., Ten, Vadim S., Thébaud, Bernard, Thornton, Claire, Tollin, Daniel J., Towbin, Jeffrey A., Truog, William E., III, Uhler, Kristin M., van den Akker, Chris H.P., Nicolaas van den Anker, John, van den Hoff, Maurice J.B., van Goudoever, Johannes (Hans) B., Vickers, Mark H., Vinks, Alexander A., Virgintino, Daniela, Visscher, Marty O., Vonderohe, Caitlin E., Vyas, Neha V., Wacker-Gussmann, Annette, Walch, Abby, Wallace, Megan J., Walsh, Brian H., Wambach, Jennifer A., Wang, Linda X., Warburton, David, Ward, Robert M., Watt, Kevin M., Watterberg, Kristi L., Werner, Lynne A., Wernimont, Sarah A., Wershil, Barry K., Wessels, Andy, Whitsett, Jeffrey A., Willems, Fabienne, Win, Myat Su, Wohlmuth, Christoph, Wolf, Matthias T., Wolfson, Marla R., Wong, Ronald J., Wynn, James L., Yeo, Lami, Yoder, Bradley A., Yuskaitis, Christopher J., Zabinsky, Jennifer, and Zhou, Dan

Published
2022
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39. Gentamicin Inhibits Ca2+Channel TRPV5 and Induces Calciuresis Independent of the Calcium-Sensing Receptor?Claudin-14 Pathway

Author

van Megen, Wouter H., Beggs, Megan R., An, Sung-Wan, Ferreira, Patr?cia G., Lee, Justin J., Wolf, Matthias T., Alexander, R. Todd, and Dimke, Henrik

Abstract

The antibiotic gentamicin, frequently used to treat Gram-negative bacteria infections, has significant side effects, including renal Ca2+wasting. Gentamicin has been presumed to induce calciuresis by activating the renal Ca2+-sensing receptor, which would increase expression of the pore-blocking protein claudin-14 and reduce Ca2+reabsorption in the thick ascending limb. However, this hypothesis has not been confirmed experimentally. Using a combination of mouse models with impaired Ca2+reabsorption in the proximal tubule and the thick ascending limb, we show that neither acute nor chronic gentamicin administration induces calciuresis by acting on these segments. Instead, gentamicin blocks activity of the distal nephron Ca2+channel transient receptor potential vanilloid 5 (TRPV5) and decreases calciotropic protein expression, thereby reducing distal nephron Ca2+reabsorption. These findings illuminate the mechanism underlying gentamicin-induced urinary Ca2+loss.

Published
2022
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41. A rare case of hyporeninemic hypertension: Answers.

Author

Mashmoushi, Ahmad, Choudhary, Abha, Thomas, Christie P., and Wolf, Matthias T. F.

Subjects
HYPERTENSION genetics, ADRENAL glands, ALDOSTERONE, DIFFERENTIAL diagnosis, HYPERTENSION, GENETIC mutation, RENIN
Abstract

The article presents question and answer related to what has the differential diagnosis for monogenic causes of hyporeninemic hypertension.

Published
2021
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42. Single molecule real time sequencing in ADTKD-MUC1 allows complete assembly of the VNTR and exact positioning of causative mutations

Author

Wenzel, Andrea, Altmueller, Janine, Ekici, Arif B., Popp, Bernt, Stueber, Kurt, Thiele, Holger, Pannes, Alois, Staubach, Simon, Salido, Eduardo, Nuernberg, Peter, Reinhardt, Richard, Reis, Andre, Rump, Patrick, Hanisch, Franz-Georg, Wolf, Matthias T. F., Wiesener, Michael, Huettel, Bruno, Beck, Bodo B., Wenzel, Andrea, Altmueller, Janine, Ekici, Arif B., Popp, Bernt, Stueber, Kurt, Thiele, Holger, Pannes, Alois, Staubach, Simon, Salido, Eduardo, Nuernberg, Peter, Reinhardt, Richard, Reis, Andre, Rump, Patrick, Hanisch, Franz-Georg, Wolf, Matthias T. F., Wiesener, Michael, Huettel, Bruno, and Beck, Bodo B.

Abstract

Recently, the Mucin-1 (MUC1) gene has been identified as a causal gene of autosomal dominant tubulointerstitial kidney disease (ADTKD). Most causative mutations are buried within a GC-rich 60 basepair variable number of tandem repeat (VNTR), which escapes identification by massive parallel sequencing methods due to the complexity of the VNTR. We established long read single molecule real time sequencing (SMRT) targeted to the MUC1-VNTR as an alternative strategy to the snapshot assay. Our approach allows complete VNTR assembly, thereby enabling the detection of all variants residing within the VNTR and simultaneous determination of VNTR length. We present high resolution data on the VNTR architecture for a cohort of snapshot positive (n = 9) and negative (n = 7) ADTKD families. By SMRT sequencing we could confirm the diagnosis in all previously tested cases, reconstruct both VNTR alleles and determine the exact position of the causative variant in eight of nine families. This study demonstrates that precise positioning of the causative mutation(s) and identification of other coding and noncoding sequence variants in ADTKD-MUC1 is feasible. SMRT sequencing could provide a powerful tool to uncover potential factors encoded within the VNTR that associate with intra-and interfamilial phenotype variability of MUC1 related kidney disease.

Published
2018

43. Single molecule real time sequencing in ADTKD-MUC1 allows complete assembly of the VNTR and exact positioning of causative mutations

Author

Wenzel, Andrea, primary, Altmueller, Janine, additional, Ekici, Arif B., additional, Popp, Bernt, additional, Stueber, Kurt, additional, Thiele, Holger, additional, Pannes, Alois, additional, Staubach, Simon, additional, Salido, Eduardo, additional, Nuernberg, Peter, additional, Reinhardt, Richard, additional, Reis, André, additional, Rump, Patrick, additional, Hanisch, Franz-Georg, additional, Wolf, Matthias T. F., additional, Wiesener, Michael, additional, Huettel, Bruno, additional, and Beck, Bodo B., additional

Published
2018
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44. Autosomal dominant tubulointerstitial kidney disease: diagnosis, classification, and management—A KDIGO consensus report

Author

Eckardt, Kai-Uwe, Alper, Seth L, Antignac, Corinne, Bleyer, Anthony J, Chauveau, Dominique, Dahan, Karin, Deltas, Constantinos, Hosking, Andrew, Kmoch, Stanislav, Rampoldi, Luca, Wiesener, Michael, Wolf, Matthias T, Devuyst, Olivier, University of Zurich, and Eckardt, Kai-Uwe

Subjects
2727 Nephrology, 570 Life sciences, biology, 610 Medicine & health, 10052 Institute of Physiology
Published
2015
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46. Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression

Author

Zaucke, Frank, Boehnlein, Joana M., Steffens, Sarah, Polishchuk, Roman S., Rampoldi, Luca, Fischer, Andreas, Pasch, Andreas, Boehm, Christoph W. A., Baasner, Anne, Attanasio, Massimo, Hoppe, Bernd, Hopfer, Helmut, Beck, Bodo B., Sayer, John A., Hildebrandt, Friedhelm, Wolf, Matthias T. F., Zaucke, Frank, Boehnlein, Joana M., Steffens, Sarah, Polishchuk, Roman S., Rampoldi, Luca, Fischer, Andreas, Pasch, Andreas, Boehm, Christoph W. A., Baasner, Anne, Attanasio, Massimo, Hoppe, Bernd, Hopfer, Helmut, Beck, Bodo B., Sayer, John A., Hildebrandt, Friedhelm, and Wolf, Matthias T. F.

Abstract

Uromodulin (UMOD) mutations are responsible for three autosomal dominant tubulo-interstitial nephropathies including medullary cystic kidney disease type 2 (MCKD2), familial juvenile hyperuricemic nephropathy and glomerulocystic kidney disease. Symptoms include renal salt wasting, hyperuricemia, gout, hypertension and end-stage renal disease. MCKD is part of the ‘nephronophthisis-MCKD complex', a group of cystic kidney diseases. Both disorders have an indistinguishable histology and renal cysts are observed in either. For most genes mutated in cystic kidney disease, their proteins are expressed in the primary cilia/basal body complex. We identified seven novel UMOD mutations and were interested if UMOD protein was expressed in the primary renal cilia of human renal biopsies and if mutant UMOD would show a different expression pattern compared with that seen in control individuals. We demonstrate that UMOD is expressed in the primary cilia of renal tubules, using immunofluorescent studies in human kidney biopsy samples. The number of UMOD-positive primary cilia in UMOD patients is significantly decreased when compared with control samples. Additional immunofluorescence studies confirm ciliary expression of UMOD in cell culture. Ciliary expression of UMOD is also confirmed by electron microscopy. UMOD localization at the mitotic spindle poles and colocalization with other ciliary proteins such as nephrocystin-1 and kinesin family member 3A is demonstrated. Our data add UMOD to the group of proteins expressed in primary cilia, where mutations of the gene lead to cystic kidney disease

Published
2017

48. Mucin-1 Increases Renal TRPV5 Activity In Vitro, and Urinary Level Associates with Calcium Nephrolithiasis in Patients

Author

Nie, Mingzhu, Bal, Manjot S., Yang, Zhufeng, Liu, Jie, Rivera, Carolina, Wenzel, Andrea, Beck, Bodo B., Sakhaee, Khashayar, Marciano, Denise K., Wolf, Matthias T. F., Nie, Mingzhu, Bal, Manjot S., Yang, Zhufeng, Liu, Jie, Rivera, Carolina, Wenzel, Andrea, Beck, Bodo B., Sakhaee, Khashayar, Marciano, Denise K., and Wolf, Matthias T. F.

Abstract

Hypercalciuria is a major risk factor for nephrolithiasis. We previously reported that Uromodulin (UMOD) protects against nephrolithiasis by upregulating the renal calcium channel TRPV5. This channel is crucial for calcium reabsorption in the distal convoluted tubule (DCT). Recently, mutations in the gene encoding Mucin-1 (MUC1) were found to cause autosomal dominant tubulointerstitial kidney disease, the same disease caused by UMOD mutations. Because of the similarities between UMOD and MUC1 regarding associated disease phenotype, protein structure, and function as a cellular barrier, we examined whether urinary MUC1 also enhances TRPV5 channel activity and protects against nephrolithiasis. We established a semiquantitative assay for detecting MUC1 in human urine and found that, compared with controls (n=12), patients (n=12) with hypercalciuric nephrolithiasis had significantly decreased levels of urinary MUC1. Immunofluorescence showed MUC1 in the thick ascending limb, DCT, and collecting duct. Applying whole cell patch-clamp recording of HEK cells, we found that wild-type but not disease mutant MUC1 increased TRPV5 activity by impairing dynamin-2- and caveolin-1-mediated endocytosis of TRPV5. Coimmunoprecipitation confirmed a physical interaction between TRPV5 and MUC1. However, MUC1 did not increase the activity of N-glycan-deficient TRPV5. MUC1 is characterized by variable number tandem repeats (VNTRs) that bind the lectin galectin-3; galectin-3 siRNA but not galectin-1 siRNA prevented MUC1-induced upregulation of TRPV5 activity. Additionally, MUC1 lacking VNTRs did not increase TRPV5 activity. Our results suggest that MUC1 forms a lattice with the N-glycan of TRPV5 via galectin-3, which impairs TRPV5 endocytosis and increases urinary calcium reabsorption.

Published
2016

49. Autosomal dominant tubulointerstitial kidney disease: diagnosis, classification, and management—A KDIGO consensus report

Author

Eckardt, Kai-Uwe, primary, Alper, Seth L., additional, Antignac, Corinne, additional, Bleyer, Anthony J., additional, Chauveau, Dominique, additional, Dahan, Karin, additional, Deltas, Constantinos, additional, Hosking, Andrew, additional, Kmoch, Stanislav, additional, Rampoldi, Luca, additional, Wiesener, Michael, additional, Wolf, Matthias T., additional, and Devuyst, Olivier, additional

Published
2015
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