Impairment of the Hif-1α regulatory pathway in Foxn1-deficient (Foxn1-/- ) mice affects the skin wound healing process.
FASEB J
; 35(2): e21289, 2021 02.
Article
in En
| MEDLINE
| ID: mdl-33475195
Hypoxia and hypoxia-regulated factors (eg, hypoxia-inducible factor-1α [Hif-1α], factor inhibiting Hif-1α [Fih-1], thioredoxin-1 [Trx-1], aryl hydrocarbon receptor nuclear translocator 2 [Arnt-2]) have essential roles in skin wound healing. Using Foxn1-/- mice that can heal skin injuries in a unique scarless manner, we investigated the interaction between Foxn1 and hypoxia-regulated factors. The Foxn1-/- mice displayed impairments in the regulation of Hif-1α, Trx-1, and Fih-1 but not Arnt-2 during the healing process. An analysis of wounded skin showed that the skin of the Foxn1-/- mice healed in a scarless manner, displaying rapid re-epithelialization and an increase in transforming growth factor ß (Tgfß-3) and collagen III expression. An in vitro analysis revealed that Foxn1 overexpression in keratinocytes isolated from the skin of the Foxn1-/- mice led to reduced Hif-1α 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-1α.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Skin
/
Hypoxia-Inducible Factor 1, alpha Subunit
/
Forkhead Transcription Factors
/
Re-Epithelialization
Limits:
Animals
Language:
En
Journal:
FASEB J
Journal subject:
BIOLOGIA
/
FISIOLOGIA
Year:
2021
Document type:
Article
Affiliation country:
Poland
Country of publication:
United States