Investigation of the role of c-Src and MAP kinases in diabetic microangiopathy and development of the new molecular pharmacotherapy

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We investigated the possible involvement of Src tyrosine kinase and MAP kinases indiabetic microangiopathy. Angiotensin II (AII) plays an important role in insulin resistance in the vasculature. We examined the effects of PP2, a Src tyrosine kinase inhibitor and Src siRNA for Src gene silencing on AII-induced rat aortic smooth muscle cell (RASMC) migration. We found that PP2 and Src siRNA both inhibited AII-induced ERK1/2 and JNK activation in RASMC. We also found that both PP2 and Src siRNA strongly inhibited AII-induced RASMC migration. From these findings, it was inferred that direct inhibition of Src may be an effective option for vascular smooth muscle cell growth and migration. Pharmacological or genetic inhibition of Src may be an additional strategy to renin-angiotensin blockade for AII involved insulin resistance such as diabetic microangiopathy.