title: Essential role of krüppel-like factor 5 during tumor necrosis factor α-induced phenotypic conversion of vascular smooth muscle cells.
abstract: Tumor necrosis factor α (TNFα) plays an essential role in the regulation of vascular smooth muscle cell (VSMC) phenotype. In the present study, we provide evidence that krüppel-like factor 5 (KLF5) plays an essential role in TNFα-induced phenotypic conversion of VSMCs. Ectopic expression of KLF5 completely blocked phenotypic conversion of VSMCs from synthetic to contractile type. In addition, stimulation of VSMCs with TNFα facilitated expression of KLF5, whereas expression of smooth muscle marker genes such as SM22α and smooth muscle actin (SMA) was significantly down-regulated. TNFα significantly enhanced the promoter activity of KLF5 as well as mRNA level, which is significantly suppressed by the inhibition of the MAPK pathway. Silencing of KLF5 suppressed TNFα-induced phenotypic conversion of VSMCs, whereas overexpression of KLF5 stimulated phenotypic conversion of VSMCs and facilitated the loss of angiotensin II (AngII)-dependent contraction. Finally, overexpression of KLF5 significantly attenuated the promoter activity of SM22α and SMA. Therefore, we suggest that TNFα-dependent induction of KLF5 may play an essential role in phenotypic modulation of VSMCs.
authors.affiliation: Department of Cardiothoracic Surgery, Medical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Republic of Korea.
authors.forename: Seon Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine, Republic of Korea.
authors.forename: Sung Ji
authors.initials: SJ
authors.lastname: Yun
authors.affiliation: MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine, Republic of Korea.
authors.forename: Young Hwan
authors.initials: YH
authors.lastname: Kim
authors.affiliation: MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine, Republic of Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Ha
authors.affiliation: MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine, Republic of Korea.
authors.forename: Seo Yeon
authors.initials: SY
authors.lastname: Jin
authors.affiliation: MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine, Republic of Korea.
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Physics, Dong-A University, Busan 604-714, Republic of Korea.
authors.forename: Sun Ja
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Pusan National University School of Korean Medicine, Pusan National University, Republic of Korea.
authors.forename: Hwa Kyoung
authors.initials: HK
authors.lastname: Shin
authors.affiliation: Department of Cardiothoracic Surgery, Medical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Republic of Korea.
authors.forename: Sung Woon
authors.initials: SW
authors.lastname: Chung
authors.affiliation: MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine, Republic of Korea. Electronic address: sunsik@pusan.ac.kr.
authors.forename: Sun Sik
authors.initials: SS
authors.lastname: Bae
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D020868:Gene Silencing; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology*; D020935:MAP Kinase Signaling System; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: C492215:Klf5 protein, rat; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha
keywords: KLF; Phenotype; TNFα; VSMC