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KLF 4 is involved in ATRA‐induced mitofusin 2 expression in vascular smooth muscle cells
Author(s) -
Zhang Rui,
Han Mei,
Zheng Bin,
Li Yingjie,
Shu Yanan,
Wen Jinkun
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.833.27
Subject(s) - klf4 , chromatin immunoprecipitation , gene silencing , microbiology and biotechnology , vascular smooth muscle , small interfering rna , transcription factor , chemistry , biology , phosphorylation , gene expression , promoter , rna , gene , biochemistry , endocrinology , smooth muscle , sox2
The expression of mitofusin 2 (mfn‐2) and Krüppel‐like factor 4 (KLF4) was increased by all‐trans retinoic acid (ATRA) in vascular smooth muscle cell (VSMC) differentiation. However, the role of KLF4 and mechanism of KLF4 actions in regulating mfn‐2 expression remain unknown. In this report, Western blotting and RT‐PCR showed that overexpression of KLF4 in VSMCs increases mfn‐2 expression at both the protein and mRNA levels. Silencing of KLF4 expression by KLF4‐specific small interfering RNA (siRNA) abrogated the inducing effects of ATRA on mfn‐2 expression, indicating that KLF4 mediates ATRA‐induced mfn‐2 expression. Chromatin immunoprecipitation (ChIP) and reporter gene assays revealed that KLF4 binds directly to the mfn‐2 promoter and activates its transcription. Promoter deletion from 5' region and point mutation analysis indicated that the KLF4‐binding site 3 of mfn‐2 promoter is required for the induction of the mfn‐2 promoter activity by KLF4. Furthermore, co‐immunoprecipitation assays showed that ATRA increases the interaction of KLF4 with p300 through inducing KLF4 phosphorylation mediated by the JNK and p38 MAPK signaling, subsequently leading to the increase in KLF4 acetylation and KLF4‐mediated transcriptional activation of the mfn‐2 promoter. Our results provide a novel mechanism by which KLF4 activates mfn‐2 expression and further expand the net work of KLF4 actions in VSMCs.