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miR-200c-SUMOylated KLF4 feedback loop acts as a switch in transcriptional programs that control VSMC proliferation.

Abstract：

:The regulation of vascular smooth muscle cell (VSMC) proliferation is an important issue because it has major implications for the prevention of pathological vascular conditions. Using microRNA array screen, we found the expression levels of 200 unique miRNAs in hyperplasic tissues. Among them, miR-200c expression substantially was down-regulated. The objective of this work was to assess the function of miR-200c and SUMOylated Krϋppel-like transcription factor 4 (KLF4) in the regulation of VSMC proliferation in both cultured cells and animal models of balloon injury. Under basal conditions, we found that miR-200c inhibited the expression of KLF4 and the SUMO-conjugating enzyme Ubc9. Upon PDGF-BB treatment, Ubc9 interacted with and promoted the SUMOylation of KLF4, which allowed the recruitment of transcriptional corepressors (e.g., nuclear receptor corepressor (NCoR) and HDAC2) to the miR-200c promoter. The reduction in miR-200c levels led to increased target gene expression (e.g., Ubc9 and KLF4), which further repressed miR-200c levels and accelerated VSMC proliferation. These results demonstrate that induction of a miR-200c-SUMOylated KLF4 feedback loop is a significant aspect of the PDGF-BB proliferative response in VSMCs and that targeting Ubc9 represents a novel approach for the prevention of restenosis.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Zheng B,Bernier M,Zhang XH,Suzuki T,Nie CQ,Li YH,Zhang Y,Song LL,Shi HJ,Liu Y,Zheng CY,Wen JK

doi

10.1016/j.yjmcc.2015.03.011

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

201-12

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(15)00089-9

journal_volume

82

pub_type

杂志文章

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