title: KLF5 and hhLIM cooperatively promote proliferation of vascular smooth muscle cells.
abstract: Krüppel-like factor 5 (KLF5) plays an important role in cellular proliferation and differentiation. In this study, we show that adenovirus-mediated overexpression of KLF5 increased neointimal formation, while human heart LIM protein (hhLIM) decreased neointimal formation following vascular injury. Interestingly, neointimal formation was significantly increased in the animals where both hhLIM and KLF5 were introduced, suggesting that KLF5 can reverse hhLIM function in cell proliferation on the coexpression with hhLIM. These results were also confirmed the cellular level. Further mechanistic studies suggested that PDGF-BB promoted the interaction between hhLIM and KLF5 through stimulating hhLIM binding to TGF-β control element (TCE) on the cyclin E promoter in a KLF5-dependent manner. Failure of KLF5 binding to the TCE, on the knockdown of KLF5 by transfecting siRNA, not only prevented the recruitment of hhLIM to the cyclin E promoter but also affected activation of the cyclin E promoter by KLF5. These data suggest that KLF5 reverses hhLIM function from anti-proliferation to pro-proliferation through its interaction with hhLIM on the cyclin E promoter.
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, China.
authors.forename: Hui-jing
authors.initials: HJ
authors.lastname: Shi
authors.forename: Jin-kun
authors.initials: JK
authors.lastname: Wen
authors.forename: Sui-bing
authors.initials: SB
authors.lastname: Miao
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001483:Base Sequence; D000077214:Becaplermin; D016466:CHO Cells; D049109:Cell Proliferation; D002478:Cells, Cultured; D006224:Cricetinae; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020574:Proto-Oncogene Proteins c-sis / Q000502:physiology; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019927:Cyclin E; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D018809:Proliferating Cell Nuclear Antigen; D020574:Proto-Oncogene Proteins c-sis; C090114:cysteine and glycine-rich protein 3; D000077214:Becaplermin