Extracellular and Non-Chaperone Function of Heat Shock Protein-90α Is Required for Skin Wound Healing.
Extracellular and Non-Chaperone Function of Heat Shock Protein-90α Is Required for Skin Wound Healing.
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DOI：
10.1016/j.jid.2017.08.043
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Bhatia A;O'Brien K;Guo J;Lincoln V;Kajiwara C;Chen M;Woodley DT;Udono H;Li W
尽管多年的努力和投资，有一些局部或全身药物治疗皮肤伤口。确定伤口愈合的自然驱动因素可以促进新的有效治疗方法的开发。当皮肤损伤时，创面内热休克蛋白（Hsp）90α大量增加。然而，这些Hsp 90 α蛋白的确切作用尚不清楚。一个独特的小鼠模型，缺乏细胞内ATP酶驱动的伴侣，但幸免于细胞外片段-5支持的促运动功能的Hsp 90 α的可用性，使我们能够具体测试的作用，非伴侣功能的Hsp 90 α在正常的伤口闭合。我们发现，伴侣蛋白缺陷型Hsp 90 α-Δ突变小鼠的伤口闭合率与野生型Hsp 90 α小鼠相似。我们从编码Hsp 90 α-Δ和野生型Hsp 90 α的小鼠cDNA产生重组蛋白。局部应用Hsp 90 α-Δ突变体蛋白与全长野生型Hsp 90 α蛋白一样有效地促进伤口闭合。更重要的是，通过靶向片段-5区域的单克隆抗体选择性抑制细胞外Hsp 90 α-Δ蛋白功能破坏了野生型Hsp 90 α和Hsp 90 α-Δ小鼠的正常伤口闭合。因此，本研究为非分子伴侣细胞外Hsp 90 α作为正常伤口闭合的潜在驱动因素提供了直接支持。
Despite years of effort and investment, there are few topical or systemic medications for skin wounds. Identifying natural drivers of wound healing could facilitate the development of new and effective treatments. When skin is injured, there is a massive increase of heat shock protein (Hsp) 90α inside the wound bed. The precise role for these Hsp90α proteins, however, was unclear. The availability of a unique mouse model that lacked the intracellular ATPase-driven chaperoning, but spared the extracellular fragment-5—supported pro-motility function of Hsp90α allowed us to test specifically the role of the non-chaperone function of Hsp90 α in normal wound closure. We found that the chaperone-defective Hsp90α-Δ mutant mice showed similar wound closure rate as the wild-type Hsp90α mice. We generated recombinant proteins from the mouse cDNAs encoding the Hsp90α-Δ and wild-type Hsp90α. Topical application of Hsp90α-Δ mutant protein promoted wound closure as effectively as the full-length wild-type Hsp90α protein. More importantly, selective inhibition of the extracellular Hsp90α-Δ protein function by a monoclonal antibody targeting the fragment-5 region disrupted normal wound closure in both wild-type Hsp90α and Hsp90α-Δ mice. Thus, this study provides direct support for non-chaperone, extracellular Hsp90α as a potential driver for normal wound closure.
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影响因子：
4.6
作者：
Dong H;Zou M;Bhatia A;Jayaprakash P;Hofman F;Ying Q;Chen M;Woodley DT;Li W
通讯作者：
Li W
影响因子：
16.2
作者：
Wieman, TJ;Smiell, JM;Su, YC
通讯作者：
Su, YC
影响因子：
5.3
作者：
Cheng, Chieh-Fang;Fan, Jianhua;Li, Wei
通讯作者：
Li, Wei
影响因子：
7.8
作者：
Bandyopadhyay, Balaji;Fan, Jianhua;Guan, Shengxi;Li, Yong;Chen, Mei;Woodley, David T;Li, Wei
通讯作者：
Li, Wei
影响因子：
11.4
作者：
Li, Wei;Li, Yong;Woodley, David T.
通讯作者：
Woodley, David T.