[Effect of Kruppel-like factor 2 on the migration of human liver sinusoidal endothelial cells].

[Effect of Kruppel-like factor 2 on the migration of human liver sinusoidal endothelial cells].

Zhonghua Yi Xue Za Zhi. 2018 Feb 13;98(7):527-532

Authors: Li N, Liu C, Pan DY, Tseng YZ, Zhou J, Zeng XQ, Luo TC, Chen SY

Abstract
Objective: To investigate the effect and mechanism of Kruppel-like factor 2 (KLF2) on the migration of human liver sinusoidal endothelial cells (LSEC). Methods: Cultured human LSEC were infected with different lenti-viruses to overexpress or suppress KLF2 expression (LV5-KLF2 and LV3-shKLF2, respectively), the infection efficacies were examined by real-time PCR and Western blot analysis.Transwell migration assay was used to investigate the role of KLF2 on the migration of LSEC.The mRNA and protein expression of vascular endothelial growth factor receptor-2 (VEGFR-2) were detected by real-time PCR and Western blot analysis, respectively.The expression and phosphorylation of Src, P38 MAPK, and P44/42 MAPK were detected by Western blot. Results: The up-regulation of KLF2 expression dramatically inhibited migration of treated LSEC, compared with LV5-NC and WT control cells, fewer LV5-KLF2 cells migrated to the lower side of the filter after 12 h [ (35.6±1.4), (71.3±2.4) and (69.3±1.6), P<0.001 for all comparisons]. In contrast, the down-regulation of KLF2 expression promoted the migration of LSEC, more LV3-KLF2 cells migrated to the lower side of the filter compared with the LV3-NC and WT control cells [(189.5±5.4), (83.4±2.5) and (82.2±3.4), P<0.001 for all comparisons]. Furthermore, up-regulation of KLF2 reduced the mRNA and protein expression level of VEGFR2, while down-regulation of KLF2 significantly increased its expression in LSEC.Additionally, up-regulation of KLF2 inhibited the phosphorylation of Src, P38 MAPK, and P44/42 MAPK pathway in LSEC, whereas down-regulation of KLF2 promoted the phosphorylation of those signaling pathway proteins. Conclusions: KLF2 may inhibit the migration of human LSEC through the Src/ MAPK signaling pathway.

PMID: 29495223 [PubMed - in process]

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