NDLI: Keloid-derived keratinocytes acquire a fibroblast-like appearance and an enhanced invasive capacity in a hypoxic microenvironment in vitro

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Keloid-derived keratinocytes acquire a fibroblast-like appearance and an enhanced invasive capacity in a hypoxic microenvironment in vitro

Content Provider	PubMed Central
Author	Ma, Xiaoyang Chen, Jia Bei, Xu Long, Xiao Qin, Han Zhao, Robert Chunhua Wang, Xiaojun
Copyright Year	2015
Abstract	A keloid scar is an overgrowth of dense fibrous tissue that develops around a wound. These scars are raised scars that spread beyong the margins of the orinigal wound to normal skin by invasion. Keloid tissue consists of both an epithelium and dermal fibroblasts. Recent studies have primarily focused on keloid fibroblasts; however, the precise role of keratinocytes in the invasion process of keloids remains to be identified. Hypoxia is a typical characteristic of keloid scars, as well as other solid tumors. The expression of the transcription factor, hypoxia-inducible factor-1α (HIF-1α), is mainly induced by hypoxia and is known for its ability to induce proliferative and transformative changes in cells; its expression has been shown to correlate with tumor invasion and metastasis. In the present study, we used immunohistochemistry, fluorescence staining and western blot analysis and demonstrated that HIF-1α was highly expressed in both the epithelial layer of keloid tissue specimens and in hypoxia-exposed keratinocytes, which suggested that the keloid keratinocytes underwent epithelial-to-mesenchymal transition (EMT) in vitro. The high expression of mesenchymal markers, such as as vimentin and fibronectin was confirmed, as well as the reduced expression of E-cadherin and zonula occludens-1 (ZO-1) during this process by detection at the protein and mRNA level. Moreover, siRNA targeting HIF-1α reversed the changes which had occurred in the morphology of the keratinocytes (cells had acquired a fibroblast-like appearance) and suppressed the invasive ability of the keratinocytes. In conclusion, the present findings demonstrate that the hypoxia/HIF-1α microenvironment provides a favorable environment for keloid-derived keratinocytes to adopt a fibroblast-like appearance through EMT. This transition may be responsible for the enhanced capacity of keloid keratinocytes to invade, allowing the keloids to extend beyond the wound margin.
Related Links	http://dx.doi.org/10.3892/ijmm.2015.2135
Ending Page	1256
Page Count	11
Starting Page	1246
File Format	PDF
ISSN	1791244X
e-ISSN	1791244X
Journal	International Journal of Molecular Medicine
Issue Number	5
Volume Number	35
Language	English
Publisher	D.A. Spandidos
Publisher Date	2015-05-01
Access Restriction	Open
Rights Holder	D.A. Spandidos
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Medicine

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