title: Kruppel-like factor 2 inhibit the angiogenesis of cultured human liver sinusoidal endothelial cells through the ERK1/2 signaling pathway.
abstract: Kruppel-like factor 2 (KLF2) is a crucial anti-angiogenic factor. However, its precise role in hepatic angiogenesis induced by liver sinusoidal endothelial cells (LSECs) remain unclear. This study was aimed to evaluate the effect of KLF2 on angiogenesis of LSECs and to explore the corresponding mechanism. Cultured human LSECs were infected with different lentiviruses to overexpress or suppress KLF2 expression. The CCK-8 assay, transwell migration assay and tube formation test, were used to investigate the roles of KLF2 in the proliferation, migration and vessel tube formation of LSECs, respectively. The expression and phosphorylation of ERK1/2 were detected by western blot. We discovered that the up-regulation of KLF2 expression dramatically inhibited proliferation, migration and tube formation in treated LSECs. Correspondingly, down-regulation of KLF2 expression significantly promoted proliferation, migration and tube formation in treated LSECs. Additionally, KLF2 inhibited the phosphorylation of ERK1/2 pathway, followed by the function of KLF2 in the angiogenesis of LSECs disrupted. In conclusion, KLF2 suppressed the angiogenesis of LSECs through inhibition of cell proliferation, migration, and vessel tube formation. These functions of KLF2 may be mediated through the ERK1/2 signaling pathway.
authors.affiliation: Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: zeng.xiaoqing@zs-hospital.sh.cn.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Zeng
authors.affiliation: Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: Linala.2009@163.com.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: lasikesmi@hotmail.com.
authors.forename: Du-Yi
authors.initials: DY
authors.lastname: Pan
authors.affiliation: Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: sadsadvenus@163.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Miao
authors.affiliation: Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: ma.guifen@zs-hospital.sh.cn.
authors.forename: Gui-Fen
authors.initials: GF
authors.lastname: Ma
authors.affiliation: Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: liuyimei1988@163.com.
authors.forename: Yi-Mei
authors.initials: YM
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: dianatseng14@gmail.com.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Tseng
authors.affiliation: Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: li.feng2@zs-hospital.sh.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: xu.lili3@zs-hospital.sh.cn.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Endoscopic Research of Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: chen.shiyao@zs-hospital.sh.cn.
authors.forename: Shi-Yao
authors.initials: SY
authors.lastname: Chen
mesh_terms: D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008099:Liver / Q000166:cytology* / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology*
chemical_list: C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors
keywords: Angiogenesis; ERK1/2; KLF2; Liver sinusoidal endothelial cells; Portal hypertension