Mechanisms of chronic hypoxia-induced renal cell growth.

Chronic local tissue hypoxia appears to play an important role in the initiation and progression of chronic renal disease. We examined the effect of local hypoxia on cultured renal tubular epithelial and mesangial cell proliferation, dedifferentiation, and extracellular matrix synthesis. The underlying signaling mechanisms whereby hypoxia induces renal cell growth were evaluated. The roles of protein kinase C, p38 mitogen-activated protein kinase, TGF-beta1, osteopontin, and nitric oxide were determined.