Study On The Effect Of Hedgehog Signaling Pathway In Hair Follicles On Hair Growth Cycle And Hair Regeneration In A Short Term

Hedgehog(HH)typically has three homologous genes in vertebrates:Sonic Hedgehog(Shh),Indian Hedgehog(Ihh),and Desert Hedgehog(Dhh),encoding the corresponding SHH,IHH,and DHH protein ligands,respectively.The Hedgehog signaling pathway plays an important role in the development,homeostasis and repair of various tissues.Among them,Shh plays the most important role in hair follicles and plays a key role in tissue homeostasis and wound healing.In the skin,the Shh signaling pathway is critical for maintaining stem cell numbers and regulating hair follicle and sebaceous gland development,and can regulate epithelial-mesenchymal interactions.The receptor for Shh is the product of the tumor suppressor gene Patch(Ptch).Furthermore,the PTCH protein acts as a negative regulator of Shh and in the absence of SHH,inhibits the activated Smoothened(SMO)protein,thereby blocking the expression of downstream target genes,including gli,Ptch and TGF-? family members.Dermal sheath(DS)is a layer of connective sheath connecting hair follicle epithelium and dermal tissue,which contains smooth muscle ?-actin(?-SMA)positive mesenchymal stem cells.Our previous study found that DS plays a micro-environmental regulation of hair follicle stem cells and hair cycle.And there is Hedgehog signaling in DS.However,it is unclear what effect the Hedgehog signaling in DS has on the development and cycle of hair follicles so far.In this study,?-SMA-Cre and ?-SMA-Cre ER mice were used to specifically knock out the Ptch gene in DS,resulting in up-regulation of Hedgehog signaling.It was found that adult mouse hair follicle regeneration was delayed,and this delay continued until the next hair cycle.In the round of hair cycle,further studies found that the down-regulation of TGF-?2 in the Hair germ may be the cause of this phenotype.The specific molecular mechanism requires further research.The second study in this paper is about the response of hair follicle epithelial cells to Hedgehog signaling and short-term hair regeneration.Previous studies underscore that Hedgehog signaling is essential for hair morphogenesis.However,the role of Hedgehog signaling in adult epidermal homeostasis remains unclear.This study confirms that several Hedgehog signaling componentsare enrichedin Lgr5+epidermal stem cells/precursorcells.Hedgehog signaling transducer SMO was ablated in Lgr5+epidermal stem cells/ precursorcells and hair follicle epithelial basal cells respectively.We find that responsiveness to hedgehog signaling in hair follicle epithelial cells is not associated with telogentoanagen transition,underscoring the different molecular mechanisms between development and adult tissue homeostasis.This study provides more insights into the mechanisms of hair regeneration and tissue growth.