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5 results on '"Marina Martic"'

1. Intracellular Cyclic Nucleotide Analogues Inhibit in vitro Mitogenesis and Activation of Fibroblasts Derived from Obstructed Rat Kidneys

Author

Kristen J. Kelynack, Gavin J. Becker, Marina Martic, Melanie G. Tait, Teresa Bisucci, Ian A. Darby, and Tim D. Hewitson

Subjects
medicine.medical_specialty, Physiology, 8-Bromo Cyclic Adenosine Monophosphate, Biology, Kidney, Cell morphology, Immediate-Early Proteins, Cyclic nucleotide, chemistry.chemical_compound, Internal medicine, Cyclic AMP, Genetics, medicine, Animals, Nucleotide, Fibroblast, Cyclic GMP, Cells, Cultured, chemistry.chemical_classification, Connective Tissue Growth Factor, DNA, General Medicine, Fibroblasts, Fibrosis, Actins, Rats, CTGF, Blot, Endocrinology, medicine.anatomical_structure, chemistry, Nephrology, Intercellular Signaling Peptides and Proteins, Collagen, Nucleotides, Cyclic, Myofibroblast, Cell Division, Intracellular, Ureteral Obstruction
Abstract

As several studies indirectly suggest that inhibiting the intracellular breakdown of cyclic nucleotides may inhibit fibrogenesis, this study used membrane permeable cyclic nucleotide analogues to examine the role of cAMP and cGMP signaling pathways in the regulation of renal fibroblast function. Fibroblasts were isolated by explant outgrowth culture of rat kidneys post unilateral ureteric obstruction. Subcultured cells were exposed to 10– 1,000 µM of the cyclic nucleotide analogues 8-bromo-cAMP (8br-cAMP) and 8-bromo-cGMP (8br-cGMP). Functional parameters examined included mitogenesis (thymidine incorporation), collagen synthesis (proline incorporation), myofibroblast differentiation (Western blotting for α-smooth muscle actin; α-SMA) and expression of CTGF (Northern blotting), a TGF-β1-driven immediate early response gene. Serum-stimulated mitogenesis was decreased 27 ± 4% by 100 µM 8br-cAMP (p < 0.01), 49 ± 6% by 1,000 µM 8br-cAMP (p < 0.001) and 43 ± 7% by 1,000 µM 8br-cGMP (p < 0.01). 1,000 µM 8br-cAMP and 8br-cGMP reduced basal collagen synthesis by 80 ± 5 and 60 ± 21% respectively (both p < 0.05). Maximum dose of 8br-cAMP but not 8br-cGMP inhibited basal expression of the differentiation marker α-SMA by 43 ± 33 (p < 0.05), resulted in a more rounded cell morphology and reduced expression of CTGF by 39 ± 24% (p < 0.05). Measurement of mitochondrial activity confirmed that effects were independent of cell toxicity. In conclusion, cyclic nucleotides inhibit fibrogenesis in vitro. Strategies which elevate intracellular cyclic nucleotide concentrations may therefore be therapeutically valuable in preventing the proliferation and activation of fibroblasts in progressive renal disease.

Published
2004

2. Parathyroid Hormone Has a Prosclerotic Effect on Vascular Smooth Muscle Cells

Author

Marina Martic, Melanie G. Tait, Kristen J. Kelynack, Vlado Perkovic, Gavin J. Becker, and Tim D. Hewitson

Subjects
medicine.medical_specialty, Contraction (grammar), Vascular smooth muscle, Cell division, Arteriosclerosis, Parathyroid hormone, In Vitro Techniques, Muscle, Smooth, Vascular, Pathogenesis, Fibrosis, Internal medicine, medicine, Humans, In patient, skin and connective tissue diseases, Aorta, Cells, Cultured, Uremia, Accelerated atherosclerosis, business.industry, General Medicine, medicine.disease, Peptide Fragments, Extracellular Matrix, Endocrinology, Parathyroid Hormone, Nephrology, sense organs, Cardiology and Cardiovascular Medicine, business, Cell Division, hormones, hormone substitutes, and hormone antagonists
Abstract

Although accelerated atherosclerosis and arteriosclerosis are common in patients with renal failure, the pathogenesis of these changes is poorly understood. Parathyroid hormone (PTH) levels are elevated in renal failure, and have been linked to uraemic vascular changes in some studies. We examined the in vitro effects of increasing doses of the 1–34 fragment of PTH on human aortic vascular smooth muscle cells (VSMCs). Factors examined were: (1) collagen production using tritiated hydroxyproline incorporation and transcription of procollagen α1(I) mRNA; (2) change in the surface area of collagen I lattices; (3) mRNA transcription of the collagen binding protein β1 integrin; (4) proliferation using tritiated thymidine incorporation, and (5) methyl tetrazolium salt conversion to estimate live cell number after 5 days’ exposure to PTH. PTH at a concentration of 200 pmol/l increased total collagen synthesis (188 ± 25% of control, p < 0.01) as well as transcription of procollagen α1(I) mRNA (136 ± 11% of control, p < 0.005). PTH also increased reorganisation of collagen I lattices (surface area 47 ± 8% of well for control vs. 35.7 ± 2.5 and 34.3 ± 3.0% for PTH 100 and 200 pmol/l, respectively, p = 0.02) and upregulated β1 integrin mRNA expression (160 ± 20% of control at PTH concentration of 200 pmol/l, p < 0.05). PTH had no effect on VSMC proliferation or number at doses up to 200 pmol/l. In conclusion, PTH increases production and reorganisation of collagen by VSMCs in vitro. It is possible that more aggressive control of hyperparathyroidism in patients with renal failure may help to reduce the burden of cardiovascular disease in this patient population.

Published
2003

3. Subject Index Vol. 91, 2002

Author

Hiroyuki Sasamura, Olaf Hergesell, K. Tabei, Osamu Hotta, Norio Sunagawa, Ioannis Tzanakis, Emanuela Rizzioli, Mingcai Qiu, Paul F. Laflam, Gian Marco Ghiggeri, Yasufumi Kyuden, D. Ljubanovic, M.J. Nubé, W.E.M. Schouten, Carla Carasi, Joachim Lundahl, Mariko Miyazaki, Isao Ishikawa, Yasuhiko Ueda, Kazuhiko Funabiki, Michael Nomikos, Tatsuo Kobayashi, Maria Magalhães, Manabu Asano, Takayuki Fujita, Shaul M. Shasha, Revital Shurtz-Swirski, Susana Sampaio, H. Furuya, Kefaia El-Sayed Mohamed, Mitsuhiro Satoh, A. Bihorac, Ç. Özener, Renza Cristofani, Ikue Mori-Kudo, U. Assogba, Satoshi Ogata, A.J. van Houte, Shifra Sela, Hidetake Kurihara, Maria Rita Metelli, Kayoko Nomura, Giovanni Montini, Atsushi Satomura, S. Krizanac, Rodo O. von Vigier, Morito Endo, Jürgen Floege, Lara Alonso da Silva, Yasuharu Nomura, Satoko Honda, Manuel Pestana, Hassan Abd-El-Hady Ahmed, Omar da Rosa Santos, P. Cacoub, Toshihiro Shinosaki, Ikuko Miyai, Y. Asano, Yoshiharu Nishitani, Yoshio Taguma, Chien-Liang Chen, Chizuru Ishiguro, P. Xavier, Gianluca Caridi, Marina Martic, Jean-Pierre Guignard, Maura Zanolari Calderari, Akira Saito, Hua-Chang Fang, F. A. W. Kemperman, Huiqi Qu, Atsushi Yamauchi, Hisaya Tada, Gavin J. Becker, Koji Harada, Mohamed Abel-Kader Sobh, Galal Mohamed Amer, Luisa Murer, P A Conz, Hiroyuki Ohi, Ali Moshfegh, Armando A. Mendes, Osama Gheith, Daisuke Suzuki, Fatma Elhusseini, Ciro Tetta, Eugênio Pacelle Queiroz Madeira, Yoshinobu Fuke, Takashi Uzu, Kang-Ju Chou, Savvas Kazoulis, Manuel Palacín, Ioannis Christoulakis, P. Hausfater, G. Kantarcı, Hideyuki Kurioka, Ivano Moschèn, Stefan H. Jacobson, Graziella Zacchello, Satoshi Horikoshi, Atsushi Tsuchida, Ryoko Shimizu-Hirota, Petros Hatzilias, Alberto Bettinelli, Tim D. Hewitson, Raymond T. Krediet, J.C. Piette, Jacek Borawski, S. Tokay, Takafumi Ito, Mutsuo Taiji, Ronit Geron, Makoto Watanabe, M. Schoorl, Carlo Catalano, Pia Thylén, Péter Tóth-Heyn, Ching-Bun Chen, Rajiv Kumar, Shigemi Chiba, Stefan Bröer, Takao Saruta, Mahmoud El-Baz, Yuji Fujita, E. Akoğlu, Roberto Palla, Michał Myśliwiec, Toshiki Inokuchi, Yasuhiko Tomino, Yasuhiro Akai, E. Kusano, Yukiteru Asakimori, Maria Norpoth, Shih-Yuan Hung, Yee-Hsuan Chiou, Kristen J. Kelynack, Hideo Shiiki, Alberto A.E. Bertelli, Mari Kuroda, Yoshihiko Taniguchi, Kazumasa Hamano, Massimiliano Migliori, Steven McTaggart, P. Lebon, Toshio Miyata, Vincenzo Panichi, Gunilla Halldén, Soichi Haraguchi, Mario G. Bianchetti, Po-Tsang Lee, M.P.C. Grooteman, Hideaki Nakaya, Ken Takahara, Fabio Fabbian, Yutaka Yaguchi, Florian Lang, Anna Maria Bianchi, Birgit Kallinowski, Mitchell L. Halperin, M. Inoue, Mizuo Mifune, Masayuki Iwano, Masafumi Yamato, Stefano De Pietro, Hiroshi Noguchi, Koji Kuboki, Hsiao-Min Chung, Hideto Sakai, Tomokazu Nagano, Iwan Setiawan, Surinder Cheema-Dhadli, Nobuoki Kohno, Shan Lin, M. Vrkljan, Isao Shirato, Noriaki Yorioka, Adriana MacIntyre Innocenzi, Marcella Normanno, José Gerardo Oliveira, Matsuhiko Hayashi, Y. Ando, Lambertus Arisz, Krystyna Pawlak, Galina Shapiro, Ikuo Horigome, Takashi Furuta, Y. Akai, Batya Kristal, João Ramos, Mahmoud Wageh Rasem, Alexandra Albers, Sarantos Xirakis, Sérgio Fernando Ferreira Santos, Takao Kawamura, Martin Zeier, Hiroo Noshiro, Manuela Della Vella, Daniele Taccola, Isao Ohsawa, K. Galesic, Mie Ko, Sana Sayed Gazarin, Eduardo H. Garin, Guilherme Santoro-Lopes, Mutsuko Hidaka, Luca Giovannini, and Giulietta Sbragia

Subjects
Index (economics), business.industry, Statistics, Medicine, Subject (documents), business
Published
2002

4. Contents Vol. 91, 2002

Author

Steven McTaggart, Hisaya Tada, D. Ljubanovic, Gunilla Halldén, M.J. Nubé, Marina Martic, Yasufumi Kyuden, Luisa Murer, Vincenzo Panichi, W.E.M. Schouten, Eugênio Pacelle Queiroz Madeira, Mariko Miyazaki, Yasuhiko Ueda, Hidetake Kurihara, Maria Norpoth, Guilherme Santoro-Lopes, Mutsuko Hidaka, Galal Mohamed Amer, Ali Moshfegh, Carlo Catalano, Chien-Liang Chen, Stefano De Pietro, Koji Kuboki, Ryoko Shimizu-Hirota, P. Hausfater, Susana Sampaio, Yoshinobu Fuke, Manuel Palacín, Luca Giovannini, Savvas Kazoulis, Satoshi Ogata, A.J. van Houte, Ikuo Horigome, Graziella Zacchello, Alberto Bettinelli, Batya Kristal, Tim D. Hewitson, Isao Shirato, Noriaki Yorioka, Makoto Watanabe, Renza Cristofani, Sérgio Fernando Ferreira Santos, Takao Kawamura, Y. Akai, S. Krizanac, Jacek Borawski, Maura Zanolari Calderari, Nobuoki Kohno, Marcella Normanno, Giulietta Sbragia, Iwan Setiawan, U. Assogba, Mitsuhiro Satoh, Mutsuo Taiji, Y. Asano, Mahmoud El-Baz, Daisuke Suzuki, Gavin J. Becker, Akira Saito, Giovanni Montini, Stefan Bröer, Yuji Fujita, Revital Shurtz-Swirski, Paul F. Laflam, P A Conz, Ching-Bun Chen, Ioannis Christoulakis, Toshihiro Shinosaki, Takafumi Ito, Takashi Uzu, Yasuhiro Akai, Kang-Ju Chou, G. Kantarcı, Shan Lin, Atsushi Tsuchida, Hideo Shiiki, Mari Kuroda, Atsushi Satomura, Huiqi Qu, Soichi Haraguchi, Michał Myśliwiec, Masayuki Iwano, Masafumi Yamato, M. Vrkljan, Petros Hatzilias, Yoshihiko Taniguchi, Atsushi Yamauchi, Emanuela Rizzioli, Mingcai Qiu, Mohamed Abel-Kader Sobh, Sana Sayed Gazarin, Shigemi Chiba, M. Schoorl, E. Kusano, Yukiteru Asakimori, Anna Maria Bianchi, Birgit Kallinowski, Mario G. Bianchetti, Armando A. Mendes, Yutaka Yaguchi, Isao Ishikawa, Manuel Pestana, Pia Thylén, M. Inoue, Shifra Sela, Po-Tsang Lee, Massimiliano Migliori, Jean-Pierre Guignard, Olaf Hergesell, P. Lebon, Hideto Sakai, Yee-Hsuan Chiou, Kristen J. Kelynack, Alberto A.E. Bertelli, Osamu Hotta, Shaul M. Shasha, Tomokazu Nagano, Lambertus Arisz, Martin Zeier, H. Furuya, Kefaia El-Sayed Mohamed, A. Bihorac, Ç. Özener, Lara Alonso da Silva, Hiroshi Noguchi, Toshio Miyata, Takao Saruta, E. Akoğlu, Stefan H. Jacobson, Krystyna Pawlak, Ivano Moschèn, Maria Rita Metelli, Hsiao-Min Chung, Takashi Furuta, Adriana MacIntyre Innocenzi, Yoshiharu Nishitani, Kazumasa Hamano, Manabu Asano, Mizuo Mifune, Kayoko Nomura, Tatsuo Kobayashi, Gian Marco Ghiggeri, João Ramos, Mahmoud Wageh Rasem, José Gerardo Oliveira, Hassan Abd-El-Hady Ahmed, Hiroyuki Ohi, S. Tokay, Matsuhiko Hayashi, Osama Gheith, Carla Carasi, P. Xavier, Ikue Mori-Kudo, Hiroo Noshiro, Kazuhiko Funabiki, Michael Nomikos, Chizuru Ishiguro, Ikuko Miyai, Maria Magalhães, Péter Tóth-Heyn, Satoko Honda, Manuela Della Vella, Daniele Taccola, Gianluca Caridi, Yasuharu Nomura, Hideyuki Kurioka, Joachim Lundahl, P. Cacoub, Y. Ando, Ronit Geron, Toshiki Inokuchi, Eduardo H. Garin, Galina Shapiro, Roberto Palla, Shih-Yuan Hung, Yasuhiko Tomino, Ciro Tetta, Surinder Cheema-Dhadli, Alexandra Albers, Sarantos Xirakis, Florian Lang, Mitchell L. Halperin, Hideaki Nakaya, Ken Takahara, Fabio Fabbian, Jürgen Floege, Yoshio Taguma, Koji Harada, Hua-Chang Fang, F. A. W. Kemperman, Satoshi Horikoshi, Rodo O. von Vigier, Morito Endo, Omar da Rosa Santos, Norio Sunagawa, M.P.C. Grooteman, Fatma Elhusseini, Takayuki Fujita, Raymond T. Krediet, J.C. Piette, Rajiv Kumar, Hiroyuki Sasamura, K. Tabei, Ioannis Tzanakis, K. Galesic, Mie Ko, and Isao Ohsawa

Subjects
Traditional medicine, business.industry, Medicine, business
Published
2002

5. Pentoxifylline Reduces in vitro Renal Myofibroblast Proliferation and Collagen Secretion

Author

Kristen J. Kelynack, Marina Martic, Gavin J. Becker, Eugenia Pedagogos, and Tim D. Hewitson

Subjects
medicine.medical_specialty, Phosphodiesterase Inhibitors, In Vitro Techniques, Biology, Kidney, Pentoxifylline, Rats, Sprague-Dawley, Internal medicine, medicine, Animals, Cells, Cultured, Dose-Response Relationship, Drug, Cell growth, Muscle, Smooth, Transforming growth factor beta, Fibroblasts, In vitro, Rats, medicine.anatomical_structure, Endocrinology, Nephrology, Cell culture, biology.protein, Collagen, Myofibroblast, Cell Division, medicine.drug, Explant culture
Abstract

Interstitial myofibroblasts (MF) are cells with features of both smooth muscle cells and fibroblasts. They have been universally recognized in situations of tubulointerstitial injury, where their presence has been shown to be a marker of disease progression. The objective of this study was to determine if functions of MF relevant to fibrogenesis can be modified in vitro by the phosphodiesterase inhibitor pentoxifylline (PTX). MF were obtained from sub-culture of normal rat kidney explant outgrowths maintained in DMEM + 20% fetal calf serum (FCS), supplemented with antibiotics. Cells were characterized on the basis of growth characteristics and immunohistochemistry. MF constituted >95% of cells at passage 3. Cell culture media was supplemented with the potential antagonist PTX alone (0, 1, 10, 100 μg/ml) and in combination with TGFβ1 (5 ng/ml). Population kinetics, proliferation and collagen production were determined from cell growth, [3H]thymidine incorporation and [3H]proline incorporation in collagenous proteins, respectively. Both serum-stimulated population growth and proliferation were reduced in a linear fashion by 1, 10 and 100 μg/ml PTX (all p < 0.05 versus 0 μg/ml). Effect of PTX on cell population growth was however reversible when PTX was removed. Basal collagen secretion was decreased by PTX at 10 and 100 μg/ml (p < 0.05 versus 0 μg/ml), although cell layer collagen remained unchanged. Collagen production (secreted and cell layer) was augmented by 5 ng/ml TGFβ1. These effects on collagen production were partially reduced when 100 μg/ml PTX was added. The authors conclude that myofibroblast function can be altered with agonists/antagonists. Attempts to down-regulate fibrogenic functions of MF may therefore offer a valuable therapeutic strategy.

Published
2000

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