Title:MicroRNA-136 Promotes Vascular Muscle Cell Proliferation Through the ERK1/2 Pathway by Targeting PPP2R2A in Atherosclerosis
Volume: 13
Issue: 3
Author(s): Chun-feng Zhang, Kai Kang, Xin-miao Li and Bao-dong Xie
Affiliation:
Keywords:
Atherosclerosis, microRNA, miR-136, proliferation, vascular smooth muscle cells.
Abstract: Aberrant proliferation of vascular smooth muscle cells [VSMCs] is implicated in the pathogenesis of vascular
pathologies such as atherosclerosis and restenosis. Accumulating evidences have revealed that microRNAs are involved in
cell proliferation in various pathological conditions. In the present study, we showed that miR-136 was up regulated in
human coronary atherosclerotic plaques when compared with normal coronary artery tissues. Moreover, miR-136 levels
were up regulated in proliferative vascular smooth muscle cells induced by platelet-derived growth factor [PDGF] or serum.
In cultured VSMCs, over expression of miR-136 stimulated cell proliferation. PPP2R2A was proved to be the direct
target gene of miR-136 and knockdown of PPP2R2A had a proliferative effect on VSMCs. miR-136-induced PPP2R2A
down-regulation was accompanied by increased expression of ERK1/2 phosphorylation. Inhibition of ERK1/2 abolished
the effect of miR-136 and knockdown of PPP2R2A on VSMCs proliferation. In summary, aberrant miR-136 up regulation
in atherosclerosis contributes to abnormal VSMC proliferation through suppressing the ERK1/2 pathway by targeting
PPP2R2A. Our study also suggested that specific modulation of miR-136 in human VSMCs may provide a potential approach
for the treatment of atherosclerosis.
