Departmental Papers (Dental)
Document Type
Journal Article
Date of this Version
11-2003
Publication Source
Journal of Investigative Dermatology
Volume
121
Issue
5
Start Page
1005
Last Page
1012
DOI
10.1046/j.1523-1747.2003.12564.x
Abstract
Keloids are an excessive accumulation of extracellular matrix. Although numerous studies have shown elevated plasminogen activator inhibitor-1 (PAI-1) levels in keloid fibroblasts compared with those of normal skin. Their specific mechanisms involved in the differential expression of PAI-1 in these cell types. In this study, the upregulation of PAI-1 expression is demonstrated in keloid tissues and their derived dermal fibroblasts, attesting to the persistence, if any, of fundamental differences between in vivo and in vitro paradigms. We further examined the mechanisms involved in hypoxia-induced regulation of PAI-1 gene in dermal fibroblast derived from keloid lesions and associated clinically normal peripheral skins from the same patient. Primary cultures were exposed to an environmental hypoxia or desferroxamine. We found that the hypoxia-induced elevation of PAI-1 gene appears to be regulated at both transcriptional and post-transcriptional levels in keloid fibroblasts. Furthermore, our results showed a consistent elevation of HIF-1α protein level in keloid tissues compared with their normal peripheral skin controls, implying a potential role as a biomarker for local skin hypoxia. Treatment with antisense oligonucleotides against hypoxia-inducible factor 1α (HIF-1α) led to the downregulation of steady-state levels of PAI-1 mRNA under both normoxic and hypoxic conditions. Conceivably, our results suggest that HIF-1α may be a novel therapeutic target to modulate the scar fibrosis process.
Keywords
Antisense, Desferroxamine, Half-life, HIF-1α, Hypoxia, deferoxamine, iron derivative, plasminogen activator inhibitor 1, adult, article, cell culture, clinical article, controlled study, environmental exposure, female, fibroblast, gene expression, human, human cell, human tissue, hypoxia, in vitro study, in vivo study, keloid, male, priority journal, regulatory mechanism, skin culture, transcription initiation, upregulation
Recommended Citation
Zhang, Q., Wu, Y., Ann, D. K., Messadi, D. V., Tuan, T., Kelly, A. P., Bertolami, C. N., & Le, A. D. (2003). Mechanisms of Hypoxic Regulation of Plasminogen Activator Inhibitor-1 Gene Expression in Keloid Fibroblasts. Journal of Investigative Dermatology, 121 (5), 1005-1012. http://dx.doi.org/10.1046/j.1523-1747.2003.12564.x
Included in
Oral and Maxillofacial Surgery Commons, Oral Biology and Oral Pathology Commons, Periodontics and Periodontology Commons
Date Posted: 10 February 2023
This document has been peer reviewed.
Comments
At the time of publication, author Qunzhou Zhang was affiliated with the Charles R. Drew Univ. Med. and Sci.. Currently, (s)he is a faculty member at the School of Medical Dentistry at the University of Pennsylvania.
At the time of publication, author Anh D. Le was affiliated with the Charles R. Drew Univ. Med. and Sci., and the University of Southern California, School of Dentistry. Currently, (s)he is a faculty member at the School of Medical Dentistry at the University of Pennsylvania.