[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


1. Abstract
2. Introduction
3. PAI-1 in Human Chronic Kidney Disease
4. PAI-1 in Animal Models of Kidney Disease
5. Angiotensin, PAI-1 and TGF-b 1-The Triple Threats
6. Effects of PAI-1 and PAs on Glomerulosclerosis and Fibrosis
7. Possible Organ Specific PAI-1 Effects
8. Novel Molecules and RAS-PAI-1 Interactions: Thymosin b -4 and Ac-SDKP
9. Regression of Renal Fibrosis
9.1. ECM Modulation by RAS and Aldosterone
9.2. Cell Responses Mediated by RAS and Aldosterone
9.3. Angiotensin Receptors: AT1 vs AT2
10. RAS, PAI-1 and Dysmetabolic Syndrome
11. Summary and perspective
12. Acknowledgment
13. References


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-band 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.