Ability of Double-Stranded RNA to Promote Reprogramming in Keratinocytes

[摘要] The ability to change site-specific skin identity could have numerous potential advantages in the study of skin regenerative medicine.In human skin, volar and non-volar regions are formed during development and are maintained throughout our lifetime.Previous studies demonstrated that this site-specific skin identity is regulated by dermal fibroblasts underlying different epidermal regions.However, the mechanism by which this regulation is maintained remains unclear.Here, we investigate the potential for reprogramming skin identity using double-stranded RNA analog (poly(I:C)) in co-cultures of keratinocytes and fibroblasts.To examine this, cells were cultured in the presence or absence of poly(I:C) and specific genes including KERATIN9 and WNT7b were analyzed by qRT-PCR to characterize reprogrammed skin identity.Initial experiments confirmed that KRT9 is intrinsically expressed in keratinocytes in the absence of fibroblasts, although its expression is induced by fibroblasts.We found that poly(I:C) treatment of solo-cultures stimulates KRT9 mRNA expression over an extended period of time.In addition, KRT9 was preferentially induced in co-culture with volar fibroblasts over non-volar fibroblasts.Significantly, we identified that poly(I:C) induces the WNT/β-catenin signaling pathway and elevates KRT9 expression, a novel mechanism by which poly(I:C) may modulate skin identity.These results establish poly(I:C) treatment as a viable method for KRT9 induction.Collectively, the present study provides the undiscovered effects of poly(I:C) and suggests the possibility of clinical relevance to reprogram skin identity at the stump site of amputees.

[发布机构] Johns Hopkins University

[效力级别] dsRNA

[关键词] volar;dsRNA;poly(I:C);co-culture;Biology