Mechanisms of chronic hypoxia-induced renal cell growth

Chronic local tissue hypoxia appears to play an important role in the initi ation and progression of chronic renal disease. We examined the effect of l ocal hypoxia on cultured renal tubular epithelial and mesangial cell prolif eration, dedifferentiation, and extracellular matrix synthesis. The underly ing signaling mechanisms whereby hypoxia induces renal cell growth were eva luated. The roles of protein kinase C, p38 mitogen-activated protein kinase , TGF-beta 1, osteopontin, and nitric oxide were determined.