Protein kinase C in diabetic nephropathy.

Protein kinase C is activated in numerous tissues obtained from diabetic animals and in several cultured cell systems exposed to high media glucose in vitro including glomerular mesangial cells. Several activators of protein kinase C, such as high media glucose, angiotensin II, phorbol ester, low density lipoprotein, and the thromboxane analogue U-46619, increase TGF beta bioactivity or mRNA expression and increase the synthesis of extracellular matrix proteins by mesangial cells in culture. The studies described in the present report support the hypothesis that activation of protein kinase C by thromboxane, an eicosanoid whose production is known to be elevated in diabetes, increases TGF beta production by mesangial cells in culture. TGF beta then acts to increase extracellular matrix protein synthesis through a mechanism that does not require active protein kinase C. Thus, activation of protein kinase C in the glomerulus in diabetes could contribute to mesangial expansion by stimulating active TGF beta production.