| First Author | Bhatia A | Year | 2018 |
| Journal | J Invest Dermatol | Volume | 138 |
| Issue | 2 | Pages | 423-433 |
| PubMed ID | 28942361 | Mgi Jnum | J:258433 |
| Mgi Id | MGI:6117921 | Doi | 10.1016/j.jid.2017.08.043 |
| Citation | Bhatia A, et al. (2018) Extracellular and Non-Chaperone Function of Heat Shock Protein-90alpha Is Required for Skin Wound Healing. J Invest Dermatol 138(2):423-433 |
| abstractText | 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) 90alpha inside the wound bed. The precise role for these Hsp90alpha 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 Hsp90alpha allowed us to test specifically the role of the non-chaperone function of Hsp90alpha in normal wound closure. We found that the chaperone-defective Hsp90alpha-Delta mutant mice showed similar wound closure rate as the wild-type Hsp90alpha mice. We generated recombinant proteins from the mouse cDNAs encoding the Hsp90alpha-Delta and wild-type Hsp90alpha. Topical application of Hsp90alpha-Delta mutant protein promoted wound closure as effectively as the full-length wild-type Hsp90alpha protein. More importantly, selective inhibition of the extracellular Hsp90alpha-Delta protein function by a monoclonal antibody targeting the fragment-5 region disrupted normal wound closure in both wild-type Hsp90alpha and Hsp90alpha-Delta mice. Thus, this study provides direct support for non-chaperone, extracellular Hsp90alpha as a potential driver for normal wound closure. |
