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Plasminogen activator inhibitor‐1 and diabetic nephropathy
Author(s) -
LEE HI BAHL,
HA HUNJOO
Publication year - 2005
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/j.1440-1797.2005.00449.x
Subject(s) - plasmin , diabetic nephropathy , extracellular matrix , plasminogen activator inhibitor 1 , plasminogen activator , fibrosis , medicine , kidney , endocrinology , diabetes mellitus , tissue plasminogen activator , nephropathy , cancer research , microbiology and biotechnology , biology , biochemistry , enzyme
SUMMARY: Diabetic nephropathy is characterized by excessive accumulation of extracellular matrix (ECM) in the kidney. Decreased ECM degradation as well as increased ECM synthesis plays an important role in ECM remodeling that favours tissue fibrosis. Plasminogen activator (PA)/plasmin/PA inhibitor (PAI) system is involved in ECM degradation and PAI‐1 plays a critical role in ECM remodeling in the kidney. Normal human kidneys do not express PAI‐1 but PAI‐1 is overexpressed in pathologic conditions associated with renal fibrosis including diabetic nephropathy. Reactive oxygen species mediate PAI‐1 up‐regulation in renal cells cultured under high glucose, hypoxia, and TGF‐β1. Recent studies utilizing PAI‐1 deficient mice suggest that PAI‐1 induce ECM deposition in diabetic kidney through increased ECM synthesis by TGF‐β1 up‐regulation as well as through decreased ECM degradation by suppression of plasmin and MMP‐2 activity.