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.
journal_name
Pediatr Surg Intjournal_title
Pediatric surgery internationalauthors
Scheid A,Wenger RH,Christina H,Camenisch I,Ferenc A,Stauffer UG,Gassmann M,Meuli Mdoi
10.1007/s003830050735subject
Has Abstractpub_date
2000-01-01 00:00:00pages
232-6issue
4eissn
0179-0358issn
1437-9813journal_volume
16pub_type
杂志文章abstract::This study deals with the advancement process of neuroblastoma through clinical observations and circulating tumor cell exploration. Clinical feature, tumor biology, and circulating tumor cell detected by the previously described polymerase chain reaction (PCR) method were analyzed in 31 patients with advanced neurobl...
journal_title:Pediatric surgery international
pub_type: 杂志文章
doi:10.1007/s00383-005-1503-9
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journal_title:Pediatric surgery international
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journal_title:Pediatric surgery international
pub_type: 杂志文章
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journal_title:Pediatric surgery international
pub_type: 杂志文章
doi:10.1007/s00383-015-3808-7
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journal_title:Pediatric surgery international
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journal_title:Pediatric surgery international
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journal_title:Pediatric surgery international
pub_type: 杂志文章
doi:10.1007/s00383-004-1322-4
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journal_title:Pediatric surgery international
pub_type: 杂志文章
doi:10.1007/s00383-005-1632-1
更新日期:2006-03-01 00:00:00
abstract::In the last 2 years, 29 children with nocturnal enuresis were treated in the outpatient departments of the Departments of Urology and Pediatric Surgery of the Aristotle University, Thessaloniki. There were 22 boys and 7 girls aged 7 to 12 years. The clinical examination was normal in all cases. All children had underg...
journal_title:Pediatric surgery international
pub_type: 杂志文章
doi:10.1007/s003830050317
更新日期:1998-04-01 00:00:00
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journal_title:Pediatric surgery international
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doi:10.1007/s00383-014-3632-5
更新日期:2015-01-01 00:00:00
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journal_title:Pediatric surgery international
pub_type: 杂志文章
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journal_title:Pediatric surgery international
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journal_title:Pediatric surgery international
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journal_title:Pediatric surgery international
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journal_title:Pediatric surgery international
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更新日期:1999-01-01 00:00:00
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journal_title:Pediatric surgery international
pub_type: 杂志文章,评审
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journal_title:Pediatric surgery international
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