The role of secreted heat shock protein-90 (Hsp90) in wound healing - how could it shape future therapeutics?

Expert Rev Proteomics. 2017 Aug;14(8):665-675. doi: 10.1080/14789450.2017.1355244. Epub 2017 Jul 31.

Abstract

Defects in tissue repair or wound healing pose a clinical, economic and social problem worldwide. Despite decades of studies, there have been few effective therapeutic treatments. Areas covered: We discuss the possible reasons for why growth factor therapy did not succeed. We point out the lack of human disorder-relevant animal models as another blockade for therapeutic development. We summarize the recent discovery of secreted heat shock protein-90 (Hsp90) as a novel wound healing agent. Expert commentary: Wound healing is a highly complex and multistep process that requires participations of many cell types, extracellular matrices and soluble molecules to work together in a spatial and temporal fashion within the wound microenvironment. The time that wounds remain open directly correlates with the clinical mortality associated with wounds. This time urgency makes the healing process impossible to regenerate back to the unwounded stage, rather forces it to take many shortcuts in order to protect life. Therefore, for therapeutic purpose, it is crucial to identify so-called 'driver genes' for the life-saving phase of wound closure. Keratinocyte-secreted Hsp90α was discovered in 2007 and has shown the promise by overcoming several key hurdles that have blocked the effectiveness of growth factors during wound healing.

Keywords: Wound healing; driver genes; growth factors; heat shock proteins; therapeutics.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Exosomes / metabolism
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use*
  • Wound Healing* / drug effects

Substances

  • HSP90 Heat-Shock Proteins
  • Intercellular Signaling Peptides and Proteins
  • Recombinant Proteins