Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-30
Scheid, A; Wenger, R H; Schäffer, L; Camenisch, I; Distler, O; Ferenc, A; Cristina, H G; Ryan, H E; Johnson, R S; Wagner, K F; Stauffer, U G; Bauer, C; Gassmann, M; Meuli, M (2002). Physiologically low oxygen concentrations in fetal skin regulate hypoxia-inducible factor 1 and transforming growth factor-beta3. FASEB Journal, 16(3):411-413.
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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 1alpha (HIF-1alpha) in the sheep model in vivo and performed studies on the potential relevance of HIF-1alpha 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-1alpha could be detected neither in healthy nor in wounded tissue. At GD100, in wounds with minimal scar formation, HIF-1alpha was expressed in fibroblasts and was markedly up-regulated at the wound edge. In scarring fetal wounds at GD120, HIF-1alpha was predominantly expressed in inflammatory cells. Expression of transforming growth factor beta3 (TGF-beta3), a potent antiscarring cytokine, overlapped with HIF-1a expression at GD100. HIF-1alpha-deficient mouse embryonic fibroblasts showed impaired migratory capabilities and demonstrated that TGF-beta3, but not proscarring TGF-beta1, manifests hypoxia- and HIF-1alpha-dependent regulation. In conclusion, HIF-1alpha-dependent regulation of a potent antiscarring cytokine may provide new strategies for antiscarring manipulation of wound healing.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||05 Vetsuisse Faculty > Institute of Laboratory Animal Science|
04 Faculty of Medicine > Institute of Laboratory Animal Science
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||11 Feb 2008 13:11|
|Last Modified:||09 Dec 2012 18:58|
|Publisher:||Federation of American Societies for Experimental Biology|
|Free access at:||Publisher DOI. An embargo period may apply.|
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