Function of Krüppel‑like factor 2 in the shear stress‑induced cell differentiation of endothelial progenitor cells to endothelial cells.

Abstract

The present study aimed to evaluate the effects of Krüppel‑like factor 2 (KLF2) on the differentiation of endothelial progenitor cells (EPCs) to endothelial cells (ECs) induced by shear stress, and to investigate the corresponding mechanisms. Cultured rat late EPCs were exposed to shear stress (12dyn/cm2) for different lengths of time. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to measure the initial KLF2 mRNA levels in each group. Subsequently, the EPCs were treated with anti‑integrin β1 or β3 antibodies to block integrin β1 and β3, respectively, or cytochalasin D to destroy F‑actin, and the subsequent expression levels of KLF2 in EPCs were measured. Then, KLF2 small interfering RNAs (siRNAs) were transfected into EPCs, and RT‑qPCR was used to measure the mRNA expression level of KLF2. Additionally, flow cytometry was applied to evaluate the protein levels of cluster of differentiation 31 (CD31) and the von Willebrand factor (vWF), and the regulatory effects of KLF2 in the promoter region of vWF were determined via a luciferase assay. High shear stress upregulated KLF2 expression, while blocking integrin β1/β3 or destroying F‑actin resulted in a corresponding decrease in KLF2 expression. Downregulation of KLF2 expression by siKLF2 inhibited the differentiation of EPCs to ECs under shear stress conditions, while the expression of EC‑specific markers decreased, including CD31 and vWF. Various lengths of the vWF promoter region induced vWF expression, and EPCs co‑transfected with KLF2 significantly increased the vWF expression levels compared with the group treated with vWF alone (P<0.01). In conclusion, shear stress may upregulate KLF2 expression, which may be associated with the integrin‑actin cytoskeleton system. Most importantly, the shear stress‑induced differentiation of EPCs may be mediated by KLF2.