1998 Fiscal Year Final Research Report Summary
Celluar mechanism of fibrosis in the obstructed kidney
| Project/Area Number |
09671601
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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 |
Urology
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| Research Institution | TOHOKU University |
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Principal Investigator |
FUKUZAKI Atsushi Tohoku Univ., Hospital, Lecturer, 医学部・附属病院, 講師 (70133957)
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| Co-Investigator(Kenkyū-buntansha) |
KANETO Hiroyuki Tohoku Univ, Sch of Med, Research Associate, 医学部, 助手 (00224626)
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| Project Period (FY) |
1997 – 1998
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| Keywords | kidney / fibrosis / obstruction / siqnal transduction |
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| Research Abstract |
Renal interstitial fibrosis is a common consequence of long-standing obstructive uropathy. Fibrosis likely develops due to an imbalance between extra cellular matrix synthesis and deposition and matrix degradation. The protease plasmin can degrade avariety of extra cellular matrix molecules. Plasmin generation from plasminogen is highly regulated by the interaction of plasminogen activator inhibitor-1 (PAL-i). It has recently been shown that angiotensin II acts both directly and through induction of TGF-beta to alter the PAI-1/plasmin system. We investigated PAL-i activity in the obstructed kidney and demonstrated increased PAL-i expression in the unilaterally obstructed rat kidney. The result indicates that angiotensin II dependent inhibition of plasmin system by increased PAI-1 activity may play an important role intubulointerstitial fibrosis in the obstructed kidney. In addition, we demonstrated angiotensin II dependent cytokine expression and inflammatory cell infiltration contribute to the tubulointerstitial fibrosis and progression of the disease in the human obstructed kidneys. Furthermore, we clarified persistent activation of renin-angiotensinsystem (RAS) in the patient with chronic ureteral obstruction. These results indicate that inhibition of RAS may have a key role to protect obstructed kidneys from progression of the disease.
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Research Products
(14 results)
