氯化锂诱导毛囊干细胞定向分化中Wnt信号通路介导基因的调控

背景:研究发现氯化锂有促进毛囊干细胞向毛囊上皮定向分化的作用,但其分子调节机制仍不清楚。目的:通过外源性因子氯化锂干预人毛囊干细胞,观察Wnt信号通路中主要下游分子及目的基因的改变,探讨氯化锂对毛囊干细胞定向分化的诱导作用。方法:取正常成人除皱术后的头皮,采用两步酶消化法结合手术显微镜分选毛囊干细胞,采用角蛋白10抗体-异硫氰酸荧光素鉴定毛囊干细胞。以外源性因子氯化锂干预人毛囊干细胞。结果与结论:氯化锂干预5d后可发现毛囊干细胞体积变大,核浆比减小,Wnt信号通路中β-catenin、cyclinD1表达增强,GSK3β、Tcf3表达减弱,c-myc在氯化锂浓度低时增强浓度高时减弱。提示氯化锂可影响毛囊干细胞中Wnt信号通路β-catenin、GSK3β、Tcf3、c-myc和cyclinD1的表达水平,可能对毛囊干细胞的分化起到重要作用。

Regulation of Wnt signaling pathway involved in the differentiation of hair follicle stem cells induced by lithium chloride

BACKGROUND:Previous studies showed that hair follicle stem cells(HFSCs) can undergo committed differentiation induced by lithium chloride(LiCl),but relating molecular regulation mechanism undisclosed.OBJECTIVE:To observe the changes of downstream molecules and target genes in Wnt signaling pathway during exogenous factor LiCl intervenes HFSCs and to investigate the role of LiCl in committed differentiation of HFSCs.METHODS:HFSCs were isolated from incised scalps of patients treated with rhytidectomy by two-steps enzyme digestion followed surgical microscope operation.HFSCs were subjected to antibodies-fluorescein isothiocy of cytokeratin 19 for identification.HFSCs was intervened by exogenous factor LiCl.RESULTS AND CONCLUSION:After 5 days HFSCs treated with LiCl,HFSCs volume got larger and the nucleus/cytoplasm ratio was reduced.In Wnt signaling pathway,the mRNA expression level of β-catenin and cyclinD1 increased,GSK3β and Tcf3 decreased,accompanied with c-myc increased at a lower concentration of LiCl and inversing decreased.LiCl can affect the expression level of β-catenin,GSK3β,Tcf3,c-myc and cyclinD1 involved in Wnt signal pathway,which may play an important role in HFSC differentiation.