4 years ago

Extracellular and Non-Chaperone Function of Heat Shock Protein-90alpha (Hsp90α) is Required for Skin Wound Healing.

O'Brien, Li, Guo, Chen, Kajiwara, Woodley, Udono, Bhatia, Lincoln
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 90alpha (Hsp90α) protein 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 F-5-supported pro-motility, function of Hsp90α allowed us to test specifically the role of the non-chaperone function of Hsp90α in normal wound closure. We found that the chaperone-defective Hsp90α-Δ mutant mice showed similar wound closure rate as the Hsp90α-wt mice. We generated recombinant proteins from the mouse cDNAs encoding the Hsp90α-Δ and Hsp90α-wt. Topical application of Hsp90α-Δ mutant protein promoted wound closure as effectively as the full-length Hsp90α-wt protein. More importantly, selective inhibition of the extracellular Hsp90α-Δ protein function by a monoclonal antibody targeting the F-5 region disrupted normal wound closure in both Hsp90α-wt and Hsp90α-Δ mice. Thus, this study provides direct support for non-chaperone, extracellular Hsp90α as a potential driver for normal wound closure.

Publisher URL: http://doi.org/10.1016/j.jid.2017.08.043

DOI: 10.1016/j.jid.2017.08.043

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