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

作者：Xiaoyang Ma, Jia Chen, Bei Xu, Xiao Long, Qin Han, Robert Chunhua Zhao, Xiaojun Wang · 发表于：International Journal of Molecular Medicine · 年份：2015 · DOI：10.3892/ijmm.2015.2135 · 被引用次数：67 · 研究领域：Dermatologic Treatments and Research、Wound Healing and Treatments、Skin Protection and Aging

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 (cell...