Vitamin E promotes dermal papilla cell proliferation via the lncRNA2919/STAT1 axis to activate the Hedgehog signaling...

Hair-follicle development is a key determinant of the quality and yield of Angora rabbit wool. Vitamin E (VE) has antioxidant properties and regulates cell proliferation. However, the molecular mechanism by which VE regulates hair-follicle growth is unclear. This study investigated the effects of VE on hair follicles and dermal papilla cells (DPCs) in vitro, as well as their underlying regulatory mechanism involving long noncoding RNA (lncRNA)2919, STAT1, and the Hedgehog signaling pathway. Hair follicles and DPCs were isolated and cultured. The optimal VE concentration was determined to be 50 μM. Reverse-transcription quantitative PCR, Western blotting, and CCK-8, DNA pulldown, chromatin immunoprecipitation, and dual-luciferase reporter assays revealed that VE significantly promoted both hair-follicle growth and DPC proliferation, and also regulated the expression of hair follicle-development-related genes, such as LEF1, FGF2, TGFβ1, and SFRP2, and antioxidant genes, including SOD1 and NRF2, and also enhanced the antioxidant capacity. Mechanistically, VE significantly downregulated lncRNA2919 expression, while lncRNA2919 overexpression inhibited DPC proliferation, which was reversed by VE. Furthermore, lncRNA2919 maintained STAT1 protein levels by inhibiting the proteasome-mediated degradation pathway. STAT1 was observed to bind directly to the SHH promoter and inhibit its transcription. This effect was reversed by VE via downregulation of lncRNA2919/STAT1 and subsequent activation of the Hedgehog signaling pathway. In conclusion, VE induces the proliferation of DPCs and enhances cellular antioxidant capacity by regulating the lncRNA2919/STAT1/SHH axis, thereby promoting hair-follicle growth and development. The findings provide a novel theoretical basis for understanding hair-follicle growth and the use of VE in Angora rabbits.