Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-31

Scheid, A; Wenger, R H; Christina, H; Camenisch, I; Ferenc, A; Stauffer, U G; Gassmann, M; Meuli, M (2000). Hypoxia-regulated gene expression in fetal wound regeneration and adult wound repair. Pediatric Surgery International, 16(4):232-236.

[img]Published Version
PDF - Registered users only
152kB

View at publisher

Abstract

Fetal skin wounds heal scarlessly while adult wounds scar. Fetal wound healing occurs in a physiologically hypoxic environment whereas in adult wound healing, cells have to acutely adapt to hypoxia caused by locally impaired blood supply. We examined the expression of hypoxia-inducible factor 1 (HIF-1), a potent transcriptional regulator of oxygen-dependent genes such as vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-beta), a potentially HIF-1-regulated scarring cytokine, on fetal and adult responses to wounding. Incisional skin wounds were created in four sheep fetuses (twins served as controls) and two ewes at 100 days of gestation (term = 150 days). Fetal and adult wounds as well as non-wounded control tissues were harvested 2 days post-wounding. Intraoperative arterial blood gas analyses and invasive subcutaneous pO2 measurements revealed that the fetuses were indeed hypoxic while the mothers were normoxic. Expression patterns of HIF-1alpha were investigated by Western blot analyses. HIF-1alpha expression in fetal wounds and fetal control skin was similar, whereas HIF-1alpha was only detected in adult wounds but not in adult control skin. Exposure of cultured fetal and adult dermal fibroblasts to hypoxia (1% O2) showed a marked induction of VEGF mRNA. In contrast, exposure of these cell types to hypoxia did not significantly affect TGF-beta1 mRNA expression in comparison to their normoxic controls. The presence of HIF-1alpha in fetal but not in adult normal skin indicates that HIF-1alpha might be involved in fetal skin development. Conversely, the upregulation of HIF-1alpha in adult but not early fetal wound repair might represent a pathway in the pathogenesis of scarring, since several growth factors overexpressed in, and associated, with scarring are hypoxia-inducible. Further studies need to be performed in order to identify hypoxia-regulated HIF-1alpha target genes involved in the pathogenesis of scarring.

Citations

34 citations in Web of Science®
38 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 11 Feb 2008
0 downloads since 12 months

Additional indexing

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
Language:English
Date:2000
Deposited On:11 Feb 2008 12:11
Last Modified:02 Dec 2013 03:08
Publisher:Springer
ISSN:0179-0358
Publisher DOI:10.1007/s003830050735
PubMed ID:10898220

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page