Adiponectin affects vascular smooth muscle cell proliferation and apoptosis through modulation of the mitofusin-2-mediated Ras-Raf-Erk1/2 signaling pathway

Abstract

Vascular smooth muscle cells (VSMCs) undergo cell biological changes in response to a variety of cytokines and growth factors. Adiponectin inhibits neointimal formation through suppressing the proliferation and migration of VSMCs. However, the mechanisms underlying the effect of adiponectin on VSMC proliferation and apoptosis require further investigation. The present study was designed to investigate the mechanisms of adiponectin on VSMC proliferation and apoptosis, focusing on the mitofusin‑2 (MFN2) mediated Ras‑Raf‑extracellular signal regulated kinase (Erk)1/2 signaling pathway. The results of western blot analysis revealed that adiponectin increased the expression of MFN2 in a concentration‑dependent manner. Adiponectin also suppressed VSMC proliferation and induced VSMC apoptosis. However, transfection of the VSMCs with small interfering (si)RNA, to knock down the expression of MFN2 attenuated the effect of adiponectin on VSMC proliferation and apoptosis. The decreased expression levels of Ras, phosphorlated (p)‑c‑Raf and p‑Erk1/2, observed in the VSMCs treated with adiponectin were also reversed by the transfection of the VSMCs with MFN2 siRNA to knock down the expression of MFN2. The results of the present study demonstrated for the first time, to the best of our knowledge, that adiponectin exhibits an inhibitory effect on VSMC proliferation and induces cell proliferation via regulation of the expression levels of MFN2. Adiponectin upregulated the expression of MFN2, inhibiting the Ras‑Raf‑Erk1/2 signaling pathway, which led to the inhibition of VSMC proliferation and the induction of VSMC apoptosis. The results of the present study may provide a novel basis for the therapy of vascular disease.