STAT5 Activation in the Dermal Papilla Is Important for Hair Follicle Growth Phase Induction

Abstract

Hair follicles are skin appendages that undergo periods of growth (anagen), regression (catagen), and rest (telogen) regulated by their mesenchymal component, the dermal papilla (DP). On the basis of the reports of its specific expression in the DP, we investigated signal transducer and activator of transcription (STAT5) activation during hair development and cycling. STAT5 activation in the DP began in late catagen, reaching a peak in early anagen before disappearing for the rest of the cycle. This was confirmed by the expression profile of suppressor of cytokine signaling 2, a STAT5 target in the DP. This pattern of expression starts after the first postnatal hair cycle. Quantification of hair cycling using the Flash canonical Wnt signaling in vivo bioluminescence reporter found that conditional knockout of STAT5A/B in the DP targeted through Cre-recombinase under the control of the Sox18 promoter resulted in delayed anagen entry compared with control. Microarray analysis of STAT5 deletion versus control revealed key changes in tumor necrosis factor-α, Wnt, and fibroblast growth factor ligands, known for their role in inducing anagen entry. We conclude that STAT5 activation acts as a mesenchymal switch to trigger natural anagen entry in postdevelopmental hair follicle cycling.

Integrated Analysis of Methylome and Transcriptome Changes Reveals the Underlying Regulatory Signatures Driving Curly Wool Transformation in Chinese Zhongwei Goats

“…Evidence from the transcription factor (TF) binding site analysis of the DEGs revealed the several TFs combine with the promoters of selected genes. For example, interferon regulatory factor 2 (IRF2) and signal transducer and activator of transcription 5A (STAT5A) are reported TFs that serve as mediators to regulate transcriptional processes in HF growth and skin disease (Nishio et al, 2001;Legrand et al, 2016). The protein-protein interaction (PPI) network among overlapping genes.…”

Effects of mesenchymal stem cell therapy on alopecia areata in cellular and hair follicle organ culture models

“…Activated STAT3 has been reported to be involved in wound‐induced HF neogenesis other than the inflammatory signalling cascade. Instead, we observed that increased phosphorylation of STAT1 and STAT3 by MSCT and MSCT completely offset the effect of pretreatment with IFN‐γ . Interestingly, the stimulatory effect of hHMSCs on STAT3 in IFN‐pretreated hDPCs was as high as that of IFN‐untreated hDPCs.…”

Oncogenes and morphogens: intricacies of targeted therapy in cutaneous basal cell carcinoma

“…Similarly, Hh ligand production by a perineural niche in the bulge of the hair follicle inducing the pathway directly and maintaining a subset of hair follicle stem cells could also be affected, thus modifying hair cycling and wound repair . Moreover, Hh signalling persists in the dermal papilla and maintains its identity, and it is well known that loss of dermal papilla signalling strongly affects hair follicle cycling . These observations might explain fibrous tract and loss of hair follicles over prolonged exposure to smoothened inhibitors, possibly explaining cases where regrowth of hair is not observed despite removal of Hh inhibitors.…”