title: Complement 3 activates the KLF5 gene in rat vascular smooth muscle cells.
abstract: We have shown that spontaneously hypertensive rat (SHR)-derived vascular smooth muscle cells (VSMCs) change to the synthetic phenotype and show increased expression of complement 3 (C3) and that C3 plays a role in the change to the synthetic phenotype. To determine the mechanisms underlying the effects of C3 on this phenotypic change, we examined the effects of C3a on transcription factors involved in VSMC phenotype and found that C3a increased the expression of Krüppel-like zinc-finger transcription factor 5 (KLF5) mRNA. C3a increased KLF5 promoter activity in a concentration-dependent manner. Deletion analysis of the promoter region of the KLF5 gene revealed that the region between nucleotides-991 and -699 contains the transcriptional regulatory element stimulated by C3a. C3a induced extracellular signal-regulated kinase (ERK) phosphorylation, and C3a-increased KLF5 promoter activity was completely inhibited by the MEK inhibitor U0126. These findings suggest that C3 increases KLF5 promoter activity and gene expression via ERK signaling.
authors.affiliation: Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Ooyaguchi-kami 30-1, Itabashi-ku, Tokyo 173-8610, Japan.
authors.forename: En-Hui
authors.initials: EH
authors.lastname: Yao
authors.forename: Noboru
authors.initials: N
authors.lastname: Fukuda
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ueno
authors.forename: Akiko
authors.initials: A
authors.lastname: Tsunemi
authors.forename: Morito
authors.initials: M
authors.lastname: Endo
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003176:Complement C3 / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D051381:Rats
chemical_list: D003176:Complement C3; C118391:Klf5 protein, mouse; D051741:Kruppel-Like Transcription Factors