Tissue plasminogen activator: Beyond a protease | 50876
Journal of Clinical Toxicology

Journal of Clinical Toxicology
Open Access

ISSN: 2161-0495

+44 1478 350008

Tissue plasminogen activator: Beyond a protease

International Toxicology Summit & Expo

November 26-28, 2012 Hilton San Antonio Airport, USA

Kebin Hu

Scientific Tracks Abstracts: J Clinic Toxicol

Abstract :

t PA, a member of the serine protease family, plays a pivotal role in the homeostasis of blood coagulation/fibrinolysis and matrix regulation, and is the FDA-approved first choice for ischemic stroke and acute myocardial infarction. However, its clinical usage has been significantly damped by its nonprotease-related side effects and toxicity. Our previous studies discovered that tPA is a hybrid molecule with dual functions: protease and cytokine. As a protease, tPA converts plasminogen into active plasmin and participates in the fibrinolysis and matrix degradation. As a cytokine, tPA activates numerous receptor-mediated cellular signal transduction events contributing to its undesirable side effects and toxicity. tPA as a cytokine, plays a detrimental role in the pathogenesis of kidney fibrosis through multiple molecular mechanisms: 1) induces matrix metalloproteinases production through MAPK pathway triggering the epithelial mesenchymal transition; 2) promotes the survival, proliferation, and interstitial accumulation of fibroblasts in the diseased kidneys through p90RSK signaling; 3) promotes myofibroblast activation and macrophage migration by activating integrin signals; 4) modulates inflammation via NF-�?ºB activation. It is clear that tPA mediates its renal toxicity and side effects through its cytokine functions. Thus, better understanding of the mechanisms of tPA actions will eventually lead to the development of novel therapeutic strategies targeting its cytokine functions while retaining its beneficial protease activities

Biography :

Kebin Hu, M.D., Ph.D. is current Assistant Professor of Medicine at Penn State University College of Medicine. He completed his postdoctoral training at University of Pittsburgh before he moved to the current position in 2008. Dr. Hu has published numerous scientific papers in peer-reviewed high-impact journals including J Clin Invest, J Am Soc Nephrol, Am J Pathol, and J Biol Chem. He is/was the grant reviewer for several national and international funding agencies and reviews manuscripts for numerous reputable scientific journals