Fibroblast growth factor (FGF2) is reported to affect the proliferation, differentiation, and survival abilities of stem cells. In this study, we hypothesize that FGF2 might promote the differentiation of hair follicle stem cell (HFSCs) into endothelial cells (ECs), in a manner dependent on STAT5 activation. We first treated human HFSCs with recombinant human FGF2 to determine the involvement of FGF2 in the differentiation of HFSCs. Then the expression of EC-specific markers including von Willebrand factor (vWF), VE-cadherin, CD31, FLT-1, KDR and Tie2 was evaluated using immunofluorescence and flow cytometry, while the expression of HFSC-specific markers such as K15, K19, Lgr5, Sox9 and Lhx2 was determined by flow cytometry. Next, in vitro tube formation was performed to confirm the function of FGF2, and low-density lipoprotein (LDL) uptake by ECs and HFSCs was studied by Dil-acetylated LDL assay. In addition, we transduced FGF2-treated HFSCs with constitutive-active or dominant-negative STAT5A adenovirus vectors. FGF2 up-regulated the expression of EC-specific markers, and promoted the differentiation of HFSCs into ECs, tube formation and LDL uptake. The phosphorylated STAT5 was translocated into the nucleus of HFSCs after FGF2 treatment, but this translocation was blocked by the dominant-negative STAT5A mutant. FGF2 increased the differentiation potential through the activation of STAT5 in vivo. Taken together, we find that FGF2 promotes the differentiation of HFSCs into ECs via activated STAT5, which gives a new perspective on the role of FGF2 in the development of ischemic vascular disease.

据报道，成纤维细胞生长因子（FGF2）影响干细胞的增殖，分化和存活能力。在这项研究中，我们假设FGF2可能以依赖于STAT5激活的方式促进毛囊干细胞（HFSCs）向内皮细胞（ECs）的分化。我们首先用重组人FGF2处理人HFSC，以确定FGF2参与HFSC的分化。然后使用免疫荧光和流式细胞术评估包括血管性血友病因子（vWF），VE-钙黏着蛋白，CD31，FLT-1，KDR和Tie2的EC特异性标志物的表达，而HFSC特异性标志物如K15，K19的表达通过流式细胞术确定Lgr5，Sox9和Lhx2。接下来，体外进行管形成以证实FGF2的功能，并且通过Dil-乙酰化LDL测定研究EC和HFSC的低密度脂蛋白（LDL）摄取。另外，我们用组成性活性或显性阴性STAT5A腺病毒载体转导了经FGF2处理的HFSC。FGF2上调EC特异性标志物的表达，并促进HFSCs向ECs分化，管形成和LDL摄取。经过FGF2处理后，磷酸化的STAT5易位到HFSC的核中，但是这种易位被显性负STAT5A突变体阻止。FGF2通过体内STAT5的激活增加分化潜能。综上所述，我们发现FGF2通过以下途径促进HFSCs向EC的分化 激活的STAT5，为FGF2在缺血性血管疾病发展中的作用提供了新的视角。