2002 Fiscal Year Final Research Report Summary
Molecular mechanism of nuclear hormone receptor superfamily on pancreatic fibrosis
| Project/Area Number |
12670522
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
SHIMIZU Kyoko Tokyo Women's Medical University, Dept. of Gastroenterology, Associate, 医学部, 助手 (90187451)
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| Project Period (FY) |
2000 – 2002
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| Keywords | chronic pancreatitis / fibrosis / PPAR-gamma / inhibition of cell growth / flow cytometry / nuclear hormone receptor |
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| Research Abstract |
We have previously reported that thiazolidinedione derivatives prevent the progression of chronic pancreatitis. In the present study, we show that PPARγ are functional in pancreatic stellate cells (PSC) and that PPARγ ligands prevent the progression of fibrosis in chronic pancreatitis. PSC were isolated from rat pancreas and transiently transfected with a PPAR-driven reporter gene to determine if the endogenous receptor responds to known ligands. Next, the effect of PPARγ ligands on cell proliferation was examined by MTT assays and flow cytometry, and finally, we investigated whether PPARγ ligands modify the progression of chronic pancreatitis in the WBN/Kob rat. PSC showed positive immunostaining for collagen I, III, and α-SMA in the cytoplasm, and positive immunostaining for PPARγ in the nucleus. PPARγ ligands increased expression of the reporter gene under the control of the PPAR response element, indicating that PPARγ is functionally active in these cells. In addition, PPARγ ligands inhibited cell proliferation by blocking cell cycle progression beyond the G1 phase. Progression of fibrosis in a rat model of chronic pancreatitis was markedly attenuated by administration of PPARγ ligands. In conclusion, PSC represent an important potential target for PPARγ ligands. PPARγ ligands may represent novel therapeutic agents for the treatment of chronic pancreatitis.
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