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Physiologically low oxygen concentrations determined in fetal skin regulate hypoxia‐inducible factor 1 and transforming growth factor β3
Author(s) -
Scheid Annette,
Wenger Roland H.,
Schäffer Leonhard,
Camenisch Isabelle,
Distler Oliver,
Ferenc Andrej,
Cristina Heidi,
Ryan Heather E.,
Johnson Randall S.,
Wagner Klaus F.,
Stauffer Urs G.,
Bauer Christian,
Gassmann Max,
Meuli Martin
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0496fje
Subject(s) - wound healing , fetus , hypoxia (environmental) , transforming growth factor , cytokine , hypoxia inducible factors , andrology , medicine , skin repair , in vivo , growth factor , immunology , biology , pathology , chemistry , endocrinology , oxygen , pregnancy , biochemistry , genetics , microbiology and biotechnology , organic chemistry , gene , receptor
In the first‐trimester mammalian fetus, skin wounds heal with perfect reconstitution of the dermal architecture without scar formation. Understanding environmental molecular regulation in fetal wound healing may reveal scar‐limiting therapeutical strategies for the prevention of postnatal scarring wound repair. Therefore, we performed studies on fetal skin oxygenation and skin and wound expression of hypoxia‐inducible factor 1α (HIF‐1α) in the sheep model in vivo and performed studies on the potential relevance of HIF‐1α during wound healing in vitro. Skin oxygen partial pressure levels were hypoxic throughout normal development. In nonscarring fetal skin at gestation day (GD)60, HIF‐1 α could be detected neither in healthy nor in wounded tissue. At GD100, in wounds with minimal scar formation, HIF‐1 α was expressed in fibroblasts and was markedly up‐regulated at the wound edge. In scarring fetal wounds at GD120, HIF‐1 α was predominantly expressed in inflammatory cells. Expression of transforming growth factor β3 (TGF‐β3), a potent antiscarring cytokine, overlapped with HIF‐1 α expression at GD100. HIF‐1 α‐deficient mouse embryonic fibroblasts showed impaired migratory capabilities and demonstrated that TGF‐β3, but not proscarring TGF‐β1, manifests hypoxia‐ and HIF‐1α‐dependent regulation. In conclusion, HIF‐1‐dependent regulation of a potent antiscarring cytokine may provide new strategies for antiscarring manipulation of wound healing.