MTORC1信号通路在毛囊生长期启动时特异促进毛囊干细胞增殖

Abstract

Objective To identify the time window during which the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway plays a key role in telogen-to-anagen transition of hair follicles, and to explore whether the pathway specifically promotes the proliferation of hair follicle stem cells (HFSCs) . Methods Totally, 36 newborn ICR mice were randomly and equally divided into 3 groups: RAPA-P19 group intraperitoneally injected with 5 mg·kg-1·d-1 sirolimus on days 19-24 after birth, RAPA-P21 group intraperitoneally injected with 5 mg·kg-1·d-1 sirolimus on days 21-24 after birth, and control group intraperitoneally injected with the same volume of solvent on days 19-24 after birth. Four mice were sacrificed in each group on days 22, 23 and 24 separately. Skin tissues were resected from the back, and hematoxylin-eosin staining of the skin tissues were performed followed by observation of hair follicle morphology to evaluate whether murine hair follicles progressed into the anagen phase on day 24. Immunofluorescence costaining was conducted to determine the expression and localization of mTORC1 downstream molecular marker pS6 and cell proliferation marker Ki67 on days 22 and 23. Results On day 24, hematoxylin-eosin staining showed anagen hair follicles in the control group and RAPA-P21 group, but telogen hair follicles in the RAPA-P19 group. On days 22 and 23, immunofluorescence costaining revealed positive staining for both pS6 and Ki67 in HFSCs in the control group, negative staining for both pS6 and Ki67 in the RAPA-P19 group, negative staining for pS6 and positive staining for Ki67 in the RAPA-P21 group. On day 23, epidermal cells and sebaceous gland cells in the upper hair follicle bulge were stained positively for Ki67 in all the 3 groups. Conclusion mTORC1 signaling specifically promotes the proliferation of HFSCs during telogen-to-anagen transition, but not affects proliferation of other cells in hair follicles. Key words: Hair follicle; Stem cells; Cell proliferation; Sirolimus; Hair cycle; Time window; mTORC1