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Start Over Author "Julie Venter" Journal gastroenterology
72 results on '"Julie Venter"'

1. Sa1502 – Knockout (KO) of the Melatonin Receptor, Mt2, Enhances Alcohol-Induced Ductular Reaction (DR), Biliary Senescence and Hepatic Fibrosis During Alcoholic Liver Disease (ALD)

Author

Shannon Glaser, Lixian Chen, Nan Wu, Fanyin Meng, David C. Zawieja, Tianhao Zhou, Konstantina Kyritsi, Gianfranco Alpini, Tori White, Heather Francis, Bin Gao, Adrien Guillot, Ludovica Ceci, Julie Venter, Suthat Liangpunsakul, and Lindsey Kennedy

Subjects
Senescence, Alcoholic liver disease, medicine.medical_specialty, Hepatology, business.industry, Gastroenterology, Alcohol, medicine.disease, Melatonin receptor, chemistry.chemical_compound, Endocrinology, chemistry, Internal medicine, medicine, Hepatic fibrosis, business
Published
2019

2. Sa1510 – Increased Serotonin (5HT) Biliary Synthesis Due to Enhanced Expression of Tryptophan Hydroxylase1 (TPH1) and Reduced Monoamine-Oxidase-A (MAO-A) Expression is Couple with Alcohol-Induced Liver Injury (ALI)

Author

Tianhao Zhou, Suthat Liangpunsakul, Adrien Guillot, Nan Wu, Ludovica Ceci, Fanyin Meng, Shannon Glas, Lixian Chen, Tori White, Julie Venter, Heather Francis, Bin Gao, Gianfranco Alpini, Konstantina Kyritsi, and Lindsey Kennedy

Subjects
Liver injury, medicine.medical_specialty, TPH1, Hepatology, biology, Gastroenterology, Tryptophan, Alcohol, medicine.disease, chemistry.chemical_compound, Endocrinology, chemistry, Internal medicine, medicine, biology.protein, Serotonin, Monoamine oxidase A, 5-HT receptor
Published
2019

3. 772 – Extracellular Vesicles Isolated from Cholangiocytes Lacking the Secretin/Secretin Receptor Axis Attenuate Liver Fibrosis Via Cargo Micrornas in the Mdr2-/- Mouse Model of Primary Sclerosing Cholangitis

Author

Keisaku Sato, Heather Francis, Julie Venter, Gianfranco Alpini, Lindsey Kennedy, Fanyin Meng, and Shannon Glaser

Subjects
Hepatology, Chemistry, Liver fibrosis, microRNA, Gastroenterology, medicine, Cancer research, Secretin receptor, medicine.disease, Extracellular vesicles, Primary sclerosing cholangitis, Secretin
Published
2019

4. Mo1470 – Secretin/Secretin Receptor Signaling Modulates Biliary Immunobiology and Subsequent T Cell Migration in Early Stage Primary Biliary Cholangitis (PBC)

Author

Gianfranco Alpini, Julie Venter, Fanyin Meng, Lindsey Kennedy, David C. Zawieja, Heather Francis, Nan Wu, Pietro Invernizzi, Eric Gershwin, Shannon Glaser, and Luca Fabris

Subjects
Hepatology, business.industry, Gastroenterology, Cancer research, T cell migration, Medicine, Secretin receptor, Stage (cooking), business, Secretin
Published
2019

5. Mo1428 – Role of the Aanat/Melatonin/Mt1/Mt2/Per-1 Axis in the Regulation of Biliary Damage and Liver Fibrosis in Cholestatic Mice

Author

Lindsey Kennedy, Paolo Onori, Heather Francis, Ludovica Ceci, Konstantina Kyritsi, Fanyin Meng, Nan Wu, Julie Venter, Eugenio Gaudio, Lixian Chen, Shannon Glaser, Gianfranco Alpini, Tianhao Zhou, and April O'Brien

Subjects
Melatonin, medicine.medical_specialty, Endocrinology, Hepatology, business.industry, AANAT, Internal medicine, Liver fibrosis, Gastroenterology, Medicine, business, medicine.drug
Published
2019

7. Sa1520 – Knockdown of Stimulator of Interferon Genes (STING) Reduces Biliary Senescence and Liver Inflammation and Fibrosis in the Mdr2-/- Mouse Model of Primary Sclerosing Cholangitis (PSC)

Author

Tianhao Zhou, Julie Venter, Anatoliy A. Gashev, Heather Francis, Chaodong Wu, Lixian Chen, Konstantina Kyritsi, Lindsey Kennedy, David C. Zawieja, Gianfranco Alpini, Shannon Glaser, Ludovica Ceci, Nan Wu, and Fanyin Meng

Subjects
Senescence, Gene knockdown, Hepatology, business.industry, Gastroenterology, Inflammation, medicine.disease, Primary sclerosing cholangitis, Sting, Fibrosis, Stimulator of interferon genes, medicine, Cancer research, medicine.symptom, business
Published
2019

8. Stem Cell Derived Extracellular Vesicles Inhibits Liver Inflammation and Fibrosis in a Mouse Model of Primary Sclerosing Cholangitis

Author

Sugeily Ramos-Lorenzo, Konstantina Kyritsi, Keisaku Sato, Tianhao Zhou, Kelly McDaniel, Shannon Glaser, Julie Venter, Heather Francis, Nan Wu, Fanyin Meng, and Gianfranco Alpini

Subjects
Pathology, medicine.medical_specialty, Hepatology, business.industry, Gastroenterology, Inflammation, medicine.disease, Extracellular vesicles, Primary sclerosing cholangitis, Fibrosis, Medicine, medicine.symptom, Stem cell, business
Published
2017

9. Mo1372 - Loss of the Biliary Secretin/Secretin Receptor (SCT/SR) Axis Decreases Liver Fibrosis by Enhanced Senescence of Hepatic Stellate Cells (HSCS) Through Decreased Biliary Secretion of TGFβ1

Author

Gianfranco Alpini, Julie Venter, Chaodong Wu, Antonio Franchitto, Paolo Onori, Eugenio Gaudio, Thao Giang, Konstantina Kyritsi, Tianhao Zhou, Heather Francis, Domenico Alvaro, Nan Wu, Fanyin Meng, and Shannon Glaser

Subjects
Senescence, medicine.medical_specialty, Endocrinology, Hepatology, Chemistry, Liver fibrosis, Internal medicine, Gastroenterology, medicine, Hepatic stellate cell, Biliary secretion, Secretin receptor, Secretin
Published
2018

10. 557 - Melatonin and Dark Therapy Reduce Biliary Damage, Liver Fibrosis and Angiogenesis in a Murine Model of Early Stage Primary Biliary Cholangitis (PBC)

Author

Heather Francis, Shannon Glaser, Romina Mancinelli, Paolo Onori, Pietro Invernizzi, Nan Wu, Francesca Bernuzzi, Tianhao Zhou, Gianfranco Alpini, Eugenio Gaudio, Fanyin Meng, Domenico Alvaro, Julie Venter, Antonio Franchitto, Lindsey Kennedy, Morgan Bennett, Thao Giang, and Konstantina Kyritsi

Subjects
Pathology, medicine.medical_specialty, Hepatology, business.industry, Angiogenesis, Gastroenterology, medicine.disease, Melatonin, Dark therapy, Murine model, Fibrosis, Damage liver, Medicine, Stage (cooking), business, medicine.drug
Published
2018

12. Sa1453 - Secretin Knockout Reduces Liver Damage in Alcoholic Liver Disease

Author

Sugeily Ramos-Lorenzo, Kelly McDaniel, Thao Giang, Adrien Guillot, Shannon Glaser, Heather Francis, Bin Gao, Gianfranco Alpini, Nan Wu, Konstantina Kyritsi, Fanyin Meng, and Julie Venter

Subjects
medicine.medical_specialty, Alcoholic liver disease, Endocrinology, Hepatology, business.industry, Internal medicine, Gastroenterology, medicine, Liver damage, business, medicine.disease, Secretin
Published
2018

13. Mo1377 - Pinealectomy Exacerbates Biliary Proliferation and Senescence and Liver Fibrosis During Rat Cholestatic Liver Through Decreased Biliary Melatonin Synthesis

Author

Shannon Glaser, Tianhao Zhou, Laurent Ehrlich, Gianfranco Alpini, April O'Brien, Yuyan Han, Nan Wu, Qiaobing Huang, Anh-Vu V. Nguyen, Fanyin Meng, Tori White, Konstantina Kyritsi, Julie Venter, and Lixian Chen

Subjects
Senescence, medicine.medical_specialty, Endocrinology, Hepatology, business.industry, medicine.medical_treatment, Internal medicine, Liver fibrosis, Gastroenterology, medicine, Pinealectomy, Melatonin synthesis, business
Published
2018

14. 509 - Therapeutic Effects of Extracellular Vesicles Isolated from Cholangiocytes Lacking the Secretin/Secretin Receptor (SCT/SRT) Axis on a Mouse Model of Primary Sclerosing Cholangitis

Author

Shannon Glaser, Fanyin Meng, Heather Francis, Julie Venter, Sato Keisaku, Thao Giang, and Gianfranco Alpini

Subjects
Hepatology, Chemistry, Therapeutic effect, Gastroenterology, medicine, Secretin receptor, Pharmacology, medicine.disease, Extracellular vesicles, Secretin, Primary sclerosing cholangitis
Published
2018

15. 510 - Knockout of the Substance P/Neurokinin-1 Receptor (SP/NK-1R) Axis Reduces Liver Fibrosis and Biliary Damage in the Murine Model of Primary Sclerosing Cholangitis (PSC)

Author

Shannon Glaser, Julie Venter, Nan Wu, Tianhao Zhou, Morgan Bennett, Eugenio Gaudio, Thao Giang, Gianfranco Alpini, Fanyin Meng, Tori White, Antonio Franchitto, and Paolo Onori

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, Hepatology, business.industry, Liver fibrosis, Gastroenterology, Substance P, medicine.disease, Primary sclerosing cholangitis, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, chemistry, Murine model, Tachykinin receptor 1, medicine, business
Published
2018

16. Tu1619 Blockade of Substance P Receptor attenuates Cellular Senescence and Liver Fibrosis in the Mdr2−/− Mouse Model of Primary Sclerosing Cholangitis

Author

Heather Francis, Shannon Glaser, Tianhao Zhou, Fanyin Meng, Ying Wan, Kelly McDaniel, Nan Wu, Holly Standeford, Julie Venter, and Gianfranco Alpini

Subjects
Pathology, medicine.medical_specialty, Hepatology, business.industry, Liver fibrosis, Gastroenterology, medicine, Cellular senescence, medicine.disease, business, Substance-P Receptor, Blockade, Primary sclerosing cholangitis
Published
2016

17. 745 Inhibition of Hepatic Stellate Cell Activation by Stem Cell Derived Extracellular Vesicles and microRNAs During Cholestatic Liver Injury

Author

Lindsey Kennedy, Gianfranco Alpini, Kelly McDaniel, Tianhao Zhou, Heather Francis, Julie Venter, Fanyin Meng, Shannon Glaser, Ying Wan, and Nan Wu

Subjects
Liver injury, Hepatology, Chemistry, microRNA, Gastroenterology, Hepatic stellate cell, medicine, Stem cell, medicine.disease, Hepatic stellate cell activation, Extracellular vesicles, Cell biology
Published
2016

20. Inhibition of the Gonadotropin Releasing Hormone (GNRH)/GNRHR1 Axis with Cetrorelix Reduces Hepatic Fibrosis in MDR2 -/- Mice

Author

Nan Wu, Thiao Gang, Shannon Glaser, Fanyin Meng, Keisaku Sato, Heather Francis, Julie Venter, Lindsey Kennedy, Tianhao Zhou, Konstantina Kyritsi, and Gianfranco Alpini

Subjects
medicine.medical_specialty, Endocrinology, Hepatology, Cetrorelix, business.industry, Internal medicine, Gastroenterology, medicine, Gonadotropin-releasing hormone, Hepatic fibrosis, business, medicine.drug
Published
2017

21. The Secretin/Secretin Receptor Axis is Required for Inflammatory Cell-Cell Communication Via Extracellular Vesicles Between Cholangiocytes Treated with Lipopolysaccharide

Author

Tianhao Zhou, Gianfranco Alpini, Nan Wu, Kelly McDaniel, Julie Venter, Fanyin Meng, Keisaku Sato, and Shannon Glaser

Subjects
medicine.medical_specialty, Cell signaling, Hepatology, Lipopolysaccharide, Chemistry, Gastroenterology, Extracellular vesicles, Secretin, Cell biology, chemistry.chemical_compound, Endocrinology, Internal medicine, Inflammatory cell, medicine, Secretin receptor
Published
2017

22. Depletion of Microrna-21 Reduces Infiltration of Macrophages and Neutrophils in the Liver and Attenuates Inflammatory Cytokine Production in Liver Macrophages During Experimental Cholestatic Liver Injury

Author

Fanyin Meng, Heather Francis, Tianhao Zhou, Ying Wan, Lindsey Kennedy, Kelly McDaniel, Julie Venter, Keisaku Sato, Gianfranco Alpini, Shannon Glaser, and Sugeily Ramos-Lorenzo

Subjects
Liver injury, Pathology, medicine.medical_specialty, Cytokine, Hepatology, Chemistry, medicine.medical_treatment, microRNA, Gastroenterology, medicine, medicine.disease, Infiltration (medical)
Published
2017

23. Knockout of the Secretin Receptor (SR) in Experimental Primary Sclerosing Cholangitis Reduces Biliary Hyperplasia and Liver Fibrois through Decreased Expression of Epithelial-Mesenchymal Transitions (EMT) Traits and Cellular Senescence in Cholangiocytes

Author

Paolo Onori, Fanyin Meng, Shannon Glaser, Keisaku Sato, Heather Francis, Julie Venter, Domenico Alvaro, Gianfranco Alpini, Lindsey Kennedy, Tianhao Zhou, Eugenio Gaudio, and Nan Wu

Subjects
Pathology, medicine.medical_specialty, Hepatology, Biliary hyperplasia, business.industry, Mesenchymal stem cell, Gastroenterology, Cellular senescence, liver, medicine.disease, secretin, Primary sclerosing cholangitis, medicine, Secretin receptor, biliary tree, business
Published
2017

26. 227 MiR-200b Modulates Angiogenesis and Liver Fibrosis in the Mdr2-/- Model of Primary Sclerosing Cholangitis

Author

Shannon Glaser, Julie Venter, Paolo Onori, Gianfranco Alpini, Konstantina Kyritsi, Holly Standeford, Heather Francis, Chad Hall, Eugenio Gaudio, Fanyin Meng, Nan Wu, and Antonio Franchitto

Subjects
Pathology, medicine.medical_specialty, Hepatology, Angiogenesis, business.industry, Liver fibrosis, Gastroenterology, medicine, Mir 200c, medicine.disease, business, Primary sclerosing cholangitis
Published
2016

28. 653 microRNA-34a Regulates Alcoholic Hepatitis Through SIRT1/NF-kappa;B Pathway

Author

Heather Francis, Tianhao Zhou, Julie Venter, Haibo Bai, Ying Wan, Nan Wu, Shannon Glaser, Fanyin Meng, Gianfranco Alpini, and Kelly McDaniel

Subjects
Hepatology, business.industry, MicroRNA 34a, Gastroenterology, Cancer research, Medicine, Alcoholic hepatitis, NFKB1, business, medicine.disease
Published
2016

29. Tu1694 Regulation of Cellular Senescence Associated Liver Fibrosis By Melatonin in Cholestatic Liver Injury

Author

Nan Wu, Chad Hall, Konstantina Kyritsi, Gianfranco Alpini, Lindsey Kennedy, Heather Francis, Tianhao Zhou, Shannon Glaser, Julie Venter, and Fanyin Meng

Subjects
Liver injury, medicine.medical_specialty, Hepatology, business.industry, Liver fibrosis, Gastroenterology, Cellular senescence, medicine.disease, Melatonin, Endocrinology, Internal medicine, medicine, business, medicine.drug
Published
2016

30. Tu1618 Treatment of Biliary Injury With Small Cholangiocyte Therapy Decreases Stellate Cell Activation via Mediation of Cellular Senescence

Author

Nan Wu, Heather Francis, Gianfranco Alpini, Fanyin Meng, Shannon Glaser, Julie Venter, Tianhao Zhou, Ying Wan, and Kelly McDaniel

Subjects
medicine.medical_specialty, Hepatology, business.industry, Gastroenterology, Cellular senescence, Cholangiocyte, Biliary injury, Endocrinology, Internal medicine, Mediation, Hepatic stellate cell, medicine, Cancer research, business
Published
2016

32. 750 Melatonin Therapy Reduces Biliary Proliferation and Hepatic Fibrosis in the Mdr2−/− Mouse Model of Primary Sclerosing Cholangitis (PSC) By Decreased Expression of miR-200b and Angiogenic Factors

Author

Shannon Glaser, Eugenio Gaudio, Sharon DeMorrow, Fanyin Meng, Heather Francis, Nan Wu, Gianfranco Alpini, Antonio Franchitto, Paolo Onori, Holly Standeford, and Julie Venter

Subjects
Melatonin, Pathology, medicine.medical_specialty, Hepatology, business.industry, Gastroenterology, Medicine, Mir 200c, business, Hepatic fibrosis, medicine.disease, medicine.drug, Primary sclerosing cholangitis
Published
2016

35. 457 Impact of MT2 Melatonin Receptor Deletion on Cellular Senescence in Cholangiocytes Isolated From Mice After Cholestatic Liver Injury

Author

Heather Francis, Shannon Glaser, Debolina Ray, Gianfranco Alpini, Tami Annable, Fanyin Meng, Holly Standeford, Shanika Avila, Yuyan Han, Julie Venter, Ying Wan, and Nan Wu

Subjects
medicine.medical_specialty, animal structures, TUNEL assay, Hepatology, Oncogene, Gastroenterology, Biology, medicine.disease_cause, Melatonin receptor, Endocrinology, Downregulation and upregulation, Apoptosis, Internal medicine, embryonic structures, Genetic model, medicine, Cancer research, Carcinogenesis, Protein kinase B
Abstract

A S L D A b st ra ct s BGJ398, a pan-FGFR inhibitor currently being employed in human trials, resulted in a significant increase in cellular apoptosis. Tumor tissue from mice sacrificed 10 weeks after biliary oncogene transduction of AKT and YAP also demonstrated increased expression of FGFR 1-4. BGJ398 treatment resulted in a significant reduction in tumor burden and increase in tumor cell apoptosis as assessed by the TUNEL assay in our mouse model of CCA. In Conclusion, YAP is a critical oncogene in CCA and promotes biliary carcinogenesis, in part, via upregulation of FGFR. In a murine genetic model of CCA, the FGFR specific inhibitor BGJ398 significantly reduces tumor burden by inducing apoptosis. Thus, inhibition of FGFR represents a promising therapeutic approach in YAP-driven human CCA.

Published
2015

37. 236 miR-34a Regulates Cellular Senescence in Activated Hepatic Stellate Cells During Alcohol Induced Hepatic Injury

Author

Yuyan Han, Julie Venter, Gianfranco Alpini, Shannon Glaser, Tami Annable, Kelly McDaniel, Fanyin Meng, Heather Francis, Ying Wan, and Nan Wu

Subjects
Hepatology, biology, urogenital system, Gastroenterology, Cellular senescence, Alcohol, medicine.disease, Molecular biology, chemistry.chemical_compound, nervous system, chemistry, Gene expression, Glial cell line-derived neurotrophic factor, biology.protein, medicine, Hepatic stellate cell, Steatosis, Gene
Abstract

A S L D A b st ra ct s GDNF suppresses expression of genes associated with hepatic steatosis Real-time PCR analyses of gene expression in liver from WT and GDNF Tg mice maintained on RD or HFD for 12 weeks. Plotted are means + SEM. *, P 5 mice per group.

Published
2015

38. 459 Inhibition of the Secretin/Secretin Receptor Axis Attenuates Biliary Fibrosis During Cholestasis

Author

Allyson K. Martínez, Nan Wu, Yuyan Han, Shanika Avila, Shannon Glaser, Fanyin Meng, Julie Venter, Holly Standeford, Gianfranco Alpini, and April O'Brien

Subjects
animal structures, TUNEL assay, Hepatology, Oncogene, business.industry, Gastroenterology, medicine.disease_cause, Downregulation and upregulation, Apoptosis, embryonic structures, Genetic model, medicine, Cancer research, Secretin receptor, Carcinogenesis, business, Protein kinase B
Abstract

A S L D A b st ra ct s BGJ398, a pan-FGFR inhibitor currently being employed in human trials, resulted in a significant increase in cellular apoptosis. Tumor tissue from mice sacrificed 10 weeks after biliary oncogene transduction of AKT and YAP also demonstrated increased expression of FGFR 1-4. BGJ398 treatment resulted in a significant reduction in tumor burden and increase in tumor cell apoptosis as assessed by the TUNEL assay in our mouse model of CCA. In Conclusion, YAP is a critical oncogene in CCA and promotes biliary carcinogenesis, in part, via upregulation of FGFR. In a murine genetic model of CCA, the FGFR specific inhibitor BGJ398 significantly reduces tumor burden by inducing apoptosis. Thus, inhibition of FGFR represents a promising therapeutic approach in YAP-driven human CCA.

Published
2015

40. Sa1720 Knockdown of microRNA-21 Reduces Biliary Hyperplasia and Liver Fibrosis in Cholestatic Bile Duct Ligated (BDL) Mice

Author

Heather Francis, Fanyin Meng, Yuyan Han, Laura Hargrove, Holly Standeford, Lindsey Kennedy, Gianfranco Alpini, Kelly McDaniel, and Julie Venter

Subjects
Gene knockdown, Pathology, medicine.medical_specialty, medicine.anatomical_structure, Hepatology, business.industry, Biliary hyperplasia, Bile duct, Liver fibrosis, microRNA, Gastroenterology, medicine, business
Published
2015

42. Sa1700 Inhibition of the Substance P/Neurokinin 1 Receptor Signaling Axis Reduces Cholangiocarcinoma Growth In Vivo

Author

Matthew McMillin, Syeda H. Afroze, Gabriel Frampton, Holly Standeford, Fanyin Meng, Kelly McDaniel, Shannon Glaser, Sharon DeMorrow, Yuyan Han, Julie Venter, Laura Hargrove, Heather Francis, Micheleine Guerrier, Shanika Avila, and Gianfranco Alpini

Subjects
Liver injury, medicine.medical_specialty, Hepatology, Chemistry, Gastroenterology, Cholangiocyte proliferation, Substance P, medicine.disease, Cholangiocyte, chemistry.chemical_compound, Endocrinology, In vivo, Internal medicine, Tachykinin receptor 1, medicine, Phosphorylation, Galanin
Abstract

A S L D A b st ra ct s increase in circulating Galanin in the serum. Galanin immunoreactivity was observed in both cholangiocytes and hepatocytes, whereas GalR1 was found predominantly in cholangiocytes. Systemic treatment of rats with M617 increased both CK-19 expression and IBDM in both sham and BDL-treated animals. In vitro, treatment of the mouse cholangiocyte cell line with M617 increased ERK1/2 and RSK-1 activity. There was a concomitant increase in cholangiocyte proliferation after M617 treatment that could be blocked by pretreatment with inhibitors for ERK1/2 and RSK-1. Conclusions: Data presented here demonstrate a direct stimulatory role for Galanin on cholangiocyte proliferation under physiological (sham) and pathological (BDL) conditions via a mechanism involving the activation of ERK1/2 and subsequent phosphorylation of RSK-1. Targeting Galanin or GalR1 may prove a useful strategy to regulate biliary mass during cholestatic liver injury.

Published
2014

43. 646 Translational Control of the Circadian Rhythms by MicroRNA-34a in Human Cholangiocarcinoma

Author

Shannon Glaser, Fanyin Meng, Gianfranco Alpini, Yuyan Han, Heather Francis, Kelly McDaniel, and Julie Venter

Subjects
PER2, CLOCK, endocrine system, Hepatology, MicroRNA 34a, Cell growth, microRNA, Gastroenterology, Gene silencing, Cell cycle, Biology, Cell biology, PER1
Abstract

Background & aims: Disruption of circadian rhythm is associated with cancer development and progression. MicroRNAs (miRNAs) are a class of small noncoding RNAs that trigger mRNA translation, repression or degradation. Core clock genes are the molecular basis of circadian rhythms, which include BMAL1, CLOCK, Per1/2/3 and Cry1/2. We have previously demonstrated the downregulation of Per1 expression in human cholangiocarcinoma (CCA) that was predicted as the direct target of miR-34a. Thus, we aimed to evaluate the role of deregulated circadian rhythm and related microRNAs in CCA growth. Methods: Human intraand extrahepatic CCA cells and non-malignant (H69) human cholangiocytes were serum starved for 48 hr before stimulation with 50% serum for 2 hours. The 24-hour rhythmic expression of core clock genes, such as Per1,2/3, CLOCK, BMAL1 and Cry1/2 was evaluated in CCA and H69 cells by real-time PCR. To further evaluate the role of Per1, we overexpressed Per1 by transfecting the Mz-ChA-1 cells with Per1 cDNA and empty vector. In parallel, we also silenced miR-34a expression with lenti-miR-34a ZIP with relative controls. A stably overexpressing Per1 cell line and silencing of miR-34a were established, respectively. Then, wemeasured: (i) cell proliferation byMTS assays and PCNA immunoblots; (ii) cell cycle by BD Cycle test Plus reagent kit; (iii) apoptosis by Annexin V-PE apoptosis detection kit; and (iv) cell migration and invasion by commercially available kits. We utilized luciferase assay to demonstrate that Per1 act as a target of miR-34a. Results: The 24-hour rhythmical expression of Per1 was abolished in all CCA cell lines but not in H69 cells. The rhythmic expression of BMAL1, CLOCK, Per2/3, Cry1/2 was also lost in some of the CCA cell lines tested. After overexpression of Per1, the extrahepatic CCA cell line, Mz-ChA-1, showed: (i) reduced cell proliferation (by MTS assays and PCNA immunoblots); (ii) higher G0/G1 arrest and lower G2/M arrest; (iii) enhanced apoptosis; and (iv) decreased cell invasion and migration compared to control cells. Interestingly, miR-34a was rhythmically expressed in CCA cell lines and H69. The expression level of miR-34a was higher in CCA cell lines compared to H69. Moreover, the inhibition of miR-34a decreased proliferation, migration and invasion in CCA cell lines. Dual luciferase reporter assay demonstrated that miR-34a directly targets Per1. Summary and conclusions: Disruption of circadian rhythms, miR-34a and Per1 expression may contribute to the malignant phenotypes of human cholangiocarcinoma. Our findings suggest that modulation of miR-34a-dependent Per1 expression may represent a novel therapeutic approach for human CCA.

Published
2014

47. Sa1699 Local Inhibition of Hepatic GnRH by Vivo-Morpholino Reduces Biliary Proliferation and Ameliorates the Expression of Fibrotic Markers in Cholestatic Rats

Author

Shannon Glaser, Kelly McDaniel, Laura Hargrove, Fanyin Meng, Eugenio Gaudio, Heather Francis, Antonio Franchitto, Romina Mancinelli, Sharon DeMorrow, Holly Standeford, Gianfranco Alpini, Paolo Onori, Julie Venter, and Debolina Ray

Subjects
Liver injury, medicine.medical_specialty, Hepatology, Morpholino, Chemistry, Gastroenterology, Cholangiocyte proliferation, medicine.disease, Cholangiocyte, In vitro, Endocrinology, Cell culture, Internal medicine, medicine, Phosphorylation, Galanin
Abstract

A S L D A b st ra ct s increase in circulating Galanin in the serum. Galanin immunoreactivity was observed in both cholangiocytes and hepatocytes, whereas GalR1 was found predominantly in cholangiocytes. Systemic treatment of rats with M617 increased both CK-19 expression and IBDM in both sham and BDL-treated animals. In vitro, treatment of the mouse cholangiocyte cell line with M617 increased ERK1/2 and RSK-1 activity. There was a concomitant increase in cholangiocyte proliferation after M617 treatment that could be blocked by pretreatment with inhibitors for ERK1/2 and RSK-1. Conclusions: Data presented here demonstrate a direct stimulatory role for Galanin on cholangiocyte proliferation under physiological (sham) and pathological (BDL) conditions via a mechanism involving the activation of ERK1/2 and subsequent phosphorylation of RSK-1. Targeting Galanin or GalR1 may prove a useful strategy to regulate biliary mass during cholestatic liver injury.

Published
2014

48. Sa1698 Downregulation of Menin by Mir-24-1 Increases Cholangiocarcinoma Proliferation

Author

Shannon Glaser, Terry C. Lairmore, Gergely Maté, Micheleine Guerrier, Fanyin Meng, Shanika Avila, Holly Standeford, Syeda H. Afroze, Gianfranco Alpini, Julie Venter, and Hassan Ammarzahid

Subjects
Liver injury, medicine.medical_specialty, Hepatology, Chemistry, Gastroenterology, Cholangiocyte proliferation, medicine.disease, In vitro, Cholangiocyte, Endocrinology, Downregulation and upregulation, Cell culture, Internal medicine, medicine, Phosphorylation, Galanin
Abstract

A S L D A b st ra ct s increase in circulating Galanin in the serum. Galanin immunoreactivity was observed in both cholangiocytes and hepatocytes, whereas GalR1 was found predominantly in cholangiocytes. Systemic treatment of rats with M617 increased both CK-19 expression and IBDM in both sham and BDL-treated animals. In vitro, treatment of the mouse cholangiocyte cell line with M617 increased ERK1/2 and RSK-1 activity. There was a concomitant increase in cholangiocyte proliferation after M617 treatment that could be blocked by pretreatment with inhibitors for ERK1/2 and RSK-1. Conclusions: Data presented here demonstrate a direct stimulatory role for Galanin on cholangiocyte proliferation under physiological (sham) and pathological (BDL) conditions via a mechanism involving the activation of ERK1/2 and subsequent phosphorylation of RSK-1. Targeting Galanin or GalR1 may prove a useful strategy to regulate biliary mass during cholestatic liver injury.

Published
2014

49. Su1718 Regulation of MicroRNA-21 by Interleukin-6 During Alcoholic Liver Injury

Author

Kelly McDaniel, Julie Venter, Yuyan Han, Hidekazu Tsukamoto, Gianfranco Alpini, Phillip Levine, Shannon Glaser, Heather Francis, and Fanyin Meng

Subjects
Liver injury, Hepatology, biology, business.industry, microRNA, Gastroenterology, biology.protein, Cancer research, Medicine, Interleukin 6, business, medicine.disease
Published
2013

50. Mo1778 Regulation of MicroRNAs by p53 in Functional Tumor-Initiating Cells of Human Gallbladder Cancer

Author

Yuyan Han, Kimberly K. Short-Baker, Jay Sharma, Chang-Gong Liu, Kelly McDaniel, Fanyin Meng, Heather Francis, Julie Venter, Shannon Glaser, Phillip Levine, and Gianfranco Alpini

Subjects
Oncology, medicine.medical_specialty, Hepatology, business.industry, Internal medicine, microRNA, Gastroenterology, medicine, Gallbladder cancer, medicine.disease, business, Tumor Initiating Cells
Published
2013

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