[Frontiers in Bioscience 14, 2028-2041, January 1, 2009]
PAI-1 and kidney fibrosis
Li-Jun Ma, Agnes B. Fogo
Vanderbilt University Medical Center, Department of Pathology, Nashville, Tennessee
TABLE OF CONTENTS
Substantial evidence demonstrates a link of increased plasminogen activator inhibitor-1 (PAI-1) and glomerulosclerosis and kidney fibrosis, providing a novel therapeutic option for prevention and treatment of chronic kidney diseases. Several mechanisms contributing to increased PAI-1 will be addressed, including classic key profibrotic factors such as the renin-angiotensin-system (RAS) and transforming growth factor-beta (TGF-band novel molecules identified by proteomic analysis, such as thymosin- b4. The fibrotic sequelae caused by increased PAI-1 in kidney depend not only on its classic inhibition of tissue-type and urokinase-type plasminogen activators (tPA and uPA), but also its influence on cell migration.