Resveratrol inhibits PDGF receptor mitogenic signaling in mesangial cells: role of PTP1B

摘要: Mesangioproliferative glomerulonephritis is associated with overactive PDGF receptor signal transduction. We show that the phytoalexin resveratrol dose dependently inhibits PDGF-induced DNA synthesis in mesangial cells an IC50 of 10 μM without inducing apoptosis. Remarkably, increased SIRT1 deacetylase activity induced by was not necessary for this inhibitory effect. Resveratrol significantly blocked PDGF-stimulated c-Src and Akt kinase activation, resulting reduced cyclin D1 expression attenuated pRb phosphorylation cyclin-dependent kinase-2 (CDK2) activity. Furthermore, inhibited PDGFR at PI 3 Grb-2 binding sites tyrosine-751 tyrosine-716, respectively. This deficiency resulted significant inhibition Erk1/2 MAPK Interestingly, protein tyrosine phosphatase PTP1B, which dephosphorylates tyrosine-716 on concomitant reduction PTP1B These results first time provide evidence stilbene targets to inhibit mitogenic signaling.—Venkatesan, B., Ghosh-Choudhury, N., Das, F., Mahimainathan, L., Kamat, A., Kasinath, B. S., Abboud, H. E., Choudhury, G. signaling cells: role PTP1B.