Zeng Xiao-Qing, Li Na, Pan Du-Yi, Miao Qing, Ma Gui-Fen, Liu Yi-Mei, Tseng Yu-Jen, Li Feng, Xu Li-Li, Chen Shi-Yao
Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Endoscopic Research of Zhongshan Hospital, Fudan University, Shanghai, China.
Biochem Biophys Res Commun. 2015 Sep 4;464(4):1241-1247. doi: 10.1016/j.bbrc.2015.07.113. Epub 2015 Jul 26.
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.
Kruppel样因子2(KLF2)是一种关键的抗血管生成因子。然而,其在肝窦内皮细胞(LSEC)诱导的肝脏血管生成中的具体作用仍不清楚。本研究旨在评估KLF2对LSEC血管生成的影响,并探索相应机制。用不同的慢病毒感染培养的人LSEC,以过表达或抑制KLF2的表达。分别采用CCK-8法、Transwell迁移试验和管腔形成试验研究KLF2在LSEC增殖、迁移和血管管腔形成中的作用。通过蛋白质印迹法检测ERK1/2的表达和磷酸化。我们发现,KLF2表达上调显著抑制了处理后的LSEC的增殖、迁移和管腔形成。相应地,KLF2表达下调显著促进了处理后的LSEC的增殖、迁移和管腔形成。此外,KLF2抑制ERK1/2通路的磷酸化,随后破坏了KLF2在LSEC血管生成中的功能。总之,KLF2通过抑制细胞增殖、迁移和血管管腔形成来抑制LSEC的血管生成。KLF2的这些功能可能是通过ERK1/2信号通路介导的。