| Angiotensin II-mediated activation of fibrotic pathways through ERK1/2 in rat peritoneal mesothelial cells. | |
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MedLine Citation:
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PMID: 20662702 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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INTRODUCTION: Peritoneal fibrosis is a common complication of peritoneal dialysis (PD) although the pathway involved is unclear. Of this article, angiotensin II (Ang II)-mediated upregulation of mitogen-activated protein kinase (MAPK) pathway as well as their downstream profibrotic genes including transforming growth factor (TGF)-beta1 and fibronectin (FN) was investigated. METHODS: Rat peritoneal mesothelial cells (RPMCs) were obtained by enzymatic digestion from the colic omentum. After incubated with Ang II, real-time PCR, ELISA, and Western blot analysis were used to determine RPMCs cellular and secretory (supernatants) levels of TGF-beta1, FN, tissue inhibitor of metalloproteinase-1 (TIMP-1), and plasminogen activator inhibitor-1 (PAI-1) as well as the phosphorylation of extracellular signal-regulated kinase (ERK1/2), p38 MAPK, and stress-activated protein kinase/c-Jun NH(2)-terminal kinase (JNK). We also determined the downstream pathways using the specific inhibitors including PD98059 (ERK1/2), SB230580 (p38 MAPK), SP600125 (JNK), and losartan [Ang II type-1 (AT1] receptor blocker). RESULTS: Ang II increased mRNA and protein levels of TGF-beta1, FN, TIMP-1, and PAI-1 in a time- and dose-dependent manner in RPMCs. Ang II induced a 1.5-2-fold increase in both mRNA and protein levels of the above molecules at 10 nmol/L. Ang II also upregulated the phosphorylation of ERK1/2 and p38 but not of JNK. Finally, inhibition of either AT1 or ERK1/2 was able to suppress Ang II-induced expression of FN. CONCLUSION: In cultured RPMCs, Ang II upregulated profibrotic signaling pathways through AT1-mediated ERK1/2 phosphorylation. |
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Authors:
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Jing-Yuan Xie; Nan Chen; Hong Ren; Wei-Ming Wang |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Renal failure Volume: 32 ISSN: 1525-6049 ISO Abbreviation: Ren Fail Publication Date: 2010 |
Date Detail:
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Created Date: 2010-07-28 Completed Date: 2010-12-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8701128 Medline TA: Ren Fail Country: England |
Other Details:
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Languages: eng Pagination: 871-9 Citation Subset: IM |
Affiliation:
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Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II
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physiology* Animals Cells, Cultured Epithelial Cells / physiology* Male Mitogen-Activated Protein Kinase 3 / physiology* Peritoneal Fibrosis / etiology* Peritoneum / cytology* Rats Rats, Sprague-Dawley Signal Transduction |
| Chemical | |
Reg. No./Substance:
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11128-99-7/Angiotensin II; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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