Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.04.237388v1?rss=1

Authors: Machcinska, S., Kopcewicz, M., Bukowska, J., Walendzik, K., Gawronska-Kozak, B.

Abstract:

Hypoxia and hypoxia-regulated factors [hypoxia-inducible factor-1 (Hif-1), factor inhibiting Hif-1 (Fih-1)] have essential roles in skin wound healing. Using Foxn1-/- mice that can heal skin injuries in a unique scar-free manner, we investigated the interaction between Foxn1 and hypoxia-regulated factors. Foxn1-/- mice displayed impairments in the regulation of Hif-1 and Fih-1 during the healing process. An analysis of wounded skin showed that the skin of Foxn1-/- mice healed in a scarless manner, displaying rapid re-epithelialization and an increase in Tgf{beta}-3 and collagen III expression. An in vitro analysis revealed that Foxn1 overexpression in keratinocytes isolated from the skin of Foxn1-/- mice led to reduced Hif-1 expression in normoxic but not hypoxic cultures and inhibited Fih-1 expression exclusively under hypoxic conditions. These data indicate that in the skin, Foxn1 affects hypoxia-regulated factors that control the wound healing process and suggest that under normoxic conditions, Foxn1 is a limiting factor for Hif-1.

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