Keloid-derived keratinocytes acquire a fibroblast-like appearance and an enhanced invasive capacity in a hypoxic microenvironment in vitro.
Keloid-derived keratinocytes acquire a fibroblast-like appearance and an enhanced invasive capacity in a hypoxic microenvironment in vitro.
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DOI：
10.3892/ijmm.2015.2135
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发表时间：
2015-05
影响因子：
5.4
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Ma X;Chen J;Xu B;Long X;Qin H;Zhao RC;Wang X
瘢痕疙瘩是在伤口周围形成的致密纤维组织的过度生长。这些疤痕是凸起的疤痕，通过侵入而扩散到正常皮肤的原始伤口边缘。瘢痕疙瘩组织由上皮细胞和真皮成纤维细胞组成。最近的研究主要集中在瘢痕疙瘩成纤维细胞;然而，角质形成细胞在瘢痕疙瘩侵袭过程中的确切作用仍有待确定。缺氧是瘢痕疙瘩和其他实体瘤的典型特征。转录因子低氧诱导因子-1 α（HIF-1α）的表达主要由低氧诱导，并且已知其能够诱导细胞的增殖和转化变化;其表达已被证明与肿瘤侵袭和转移相关。本研究采用免疫组化、荧光染色和western blot分析方法，证实HIF-1α在瘢痕疙瘩组织标本的上皮层和低氧暴露的角质形成细胞中均呈高表达，提示瘢痕疙瘩角质形成细胞在体外经历了上皮-间质转化（EMT）。通过蛋白质和mRNA水平的检测，证实了间充质标志物如波形蛋白和纤连蛋白的高表达，以及E-cadherin和闭合小带-1（ZO-1）在此过程中的表达减少。此外，靶向HIF-1α的siRNA逆转了角质形成细胞形态的变化（细胞获得了成纤维细胞样外观），并抑制了角质形成细胞的侵袭能力。总之，目前的研究结果表明，缺氧/HIF-1α微环境提供了一个有利的环境，瘢痕疙瘩衍生的角质形成细胞通过EMT采取成纤维细胞样的外观。这种转变可能是负责增强能力的瘢痕疙瘩角质细胞入侵，使瘢痕疙瘩延伸到伤口边缘以外。
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.
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DOI：
10.1155/2013/262796
发表时间：
2013
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Yin SY;Peng AP;Huang LT;Wang YT;Lan CW;Yang NS
通讯作者：
Yang NS
影响因子：
4.6
作者：
Chalamalasetty, Ravindra B.;Garriock, Robert J.;Yamaguchi, Terry P.
通讯作者：
Yamaguchi, Terry P.
影响因子：
2.9
作者：
Xia, W;Phan, TT;Yang, GP
通讯作者：
Yang, GP
影响因子：
5.5
作者：
Wu, YD;Zhang, QZ;Le, AD
通讯作者：
Le, AD
缺氧诱导的 Bmi1 通过 PI3K/Akt 信号促进肾小管上皮细胞间质转化和肾纤维化。
影响因子：
3.3
作者：
Du R;Xia L;Ning X;Liu L;Sun W;Huang C;Wang H;Sun S
通讯作者：
Sun S