Hypoxia regulates the expression of extracellular matrix associated proteins in equine dermal fibroblasts via HIF1
Hypoxia regulates the expression of extracellular matrix associated proteins in equine dermal fibroblasts via HIF1
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DOI：
10.1016/j.jdermsci.2011.09.006
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发表时间：
2012-01-01
影响因子：
4.6
通讯作者：
Theoret, Christine L.
中科院分区：
文献类型：
--
作者：
Deschene, Karine;Celeste, Christophe;Theoret, Christine L.
背景资料：增生性肉芽组织（Exuberant granulation tissue，EGT）是一种类似于人类瘢痕疙瘩的纤维化愈合障碍，几乎只发生在马的肢体伤口中，部分原因可能是伤口内的相对缺氧状态。目的：因此，本研究的目的是（1）评估缺氧对马皮肤成纤维细胞（EDF）增殖和凋亡的影响，（2）研究缺氧对关键细胞外基质（ECM）相关蛋白表达的影响，并确定这种影响是否依赖于缺氧诱导因子（HIF）;（3）确定来自身体或肢体的EDF是否对缺氧有不同的反应。EDFs的分离和培养，从皮肤从身体或肢体在常氧或缺氧conditions.Results：缺氧显着刺激EDF增殖，但没有影响细胞的存活。低氧模拟剂氯化钴上调COL 1A 1的表达和下调MMP 2的表达，表明ECM合成增加和营业额减少。这两种调节作用被抑制的棘霉素，表明它们是由HIF的转录调节活性介导的。没有差异，观察到EDFs来自身体或肢体的任何影响的缺氧或氯化钴，这表明EGT的发展不依赖于肢体fibroblasts.Conclusions的内在属性：我们得出结论，缺氧调节ECM重塑通过HIFI EDFs，这可能是一个重要的决定因素，在马EGT的发病机制。(C)2011年日本皮肤病学调查学会。由Elsevier爱尔兰有限公司出版。保留所有权利。
Background: Exuberant granulation tissue (EGT), a fibrotic healing disorder resembling the human keloid, occurs almost exclusively in limb wounds of horses and may be caused in part by a relative state of hypoxia within the wound.Objective: The objectives of this study were therefore to (1) assess the effects of hypoxia on equine dermal fibroblast (EDF) proliferation and apoptosis, (2) study the effects of hypoxia on the expression of key extracellular matrix (ECM) associated proteins and determine if such effects are dependent on hypoxia-inducible factor (HIF), and (3) determine if EDFs from the body or limb respond differently to hypoxia.Methods: EDFs were isolated and cultured from skin from body or limb under normoxic or hypoxic conditions for up to 7 days.Results: Hypoxia significantly stimulated EDF proliferation, but had no effect on cell survival. The hypoxia-mimetic agent CoCl2 up-regulated COL1A1 expression and down-regulated MMP2 expression, suggesting an increase in ECM synthesis and a decrease in turnover. Both regulatory effects were inhibited by the addition of echinomycin, indicating that they are mediated by the transcriptional regulatory activity of HIF. No differences were observed between EDFs originating from body or limb for any effect of hypoxia or CoCl2, suggesting that EGT development does not depend on intrinsic properties of limb fibroblasts.Conclusions: We conclude that hypoxia regulates ECM remodeling via HIFI in EDFs, and that this may be an important determinant in the pathogenesis of equine EGT. (C) 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.