Complement 3 activates the KLF5 gene in rat vascular smooth muscle cells

Biochemical and Biophysical Research Communications
En-Hui YaoKoichi Matsumoto

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.

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Citations

May 19, 2009·Cellular and Molecular Life Sciences : CMLS·Jin-Tang Dong, Ceshi Chen
May 30, 2013·Clinical and Experimental Hypertension : CHE·Kazuya IkedaKoichi Matsumoto
May 4, 2011·Atherosclerosis·Marcella MaddalunoArmando Ialenti
Apr 2, 2019·Hypertension·Cheng-Chao Ruan, Ping-Jin Gao
Dec 20, 2019·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Lan ChenMasanori Abe
Mar 27, 2020·American Journal of Physiology. Cell Physiology·Lan ChenMasanori Abe
Jan 1, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Min Soon ChoVahid Afshar-Kharghan
Dec 19, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ji Won ParkDae Youn Hwang
Feb 2, 2021·Journal of Cellular and Molecular Medicine·Jia LiMadhavi J Rane
Oct 8, 2021·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Tomoyasu OtsukiMasanori Abe

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