Extracellular and Non-Chaperone Function of Heat Shock Protein−90α Is Required for Skin Wound Healing

Ayesha Bhatia, Kathryn O'Brien, Jiacong Guo, Vadim Lincoln, Chiaki Kajiwara, Mei Chen, David T. Woodley, Heiichiro Udono, Wei Li

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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 Hsp90α 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.

Original languageEnglish
Pages (from-to)423-433
Number of pages11
JournalJournal of Investigative Dermatology
Volume138
Issue number2
DOIs
Publication statusPublished - Feb 2018

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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