Extracellular and cell surface proteases in wound healing: new players are still emerging

Eur J Dermatol. 2009 Nov-Dec;19(6):552-64. doi: 10.1684/ejd.2009.0770. Epub 2009 Jul 22.

Abstract

Tissue remodelling results from the concerted action of numerous extracellular and cell surface proteases. These act to synchronize the synthesis and degradation of the extracellular matrix with the control of cytokine activity and cell signalling in order to create appropriate environments for cell proliferation, migration and differentiation. Wound healing is a complex example of tissue remodelling that includes several steps occurring either concomitantly or successively during the process of repair: haemostasis, inflammation, angiogenesis, re-epithelialisation, granulation tissue formation, wound contraction and matrix remodelling. The main extracellular and cell surface proteases involved in wound healing are serine proteases, especially plasmin, and metalloproteases of the metzincin family (MMPs, ADAM(TS)s, tolloids, meprins, pappalysins) with cysteine proteases playing less prominent roles. Several regulatory proteins and hundreds of substrates have been identified for these proteases, either in vitro or in vivo. The aim of this review is not to present an exhaustive list of proteases and related molecules but to give an overview of the proteolytic events that are potentially relevant during tissue repair. New developments aimed at approaching a more integrative view of all the molecular events involved in tissue remodelling are also discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cysteine Proteases / metabolism
  • Extracellular Matrix / metabolism
  • Extracellular Space / metabolism
  • Fibrinolysin / metabolism
  • Fibrinolytic Agents / metabolism
  • Hemostasis / genetics
  • Humans
  • Inflammation / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Matrix Metalloproteinases / metabolism
  • Neovascularization, Physiologic / genetics
  • Peptide Hydrolases / genetics
  • Peptide Hydrolases / metabolism*
  • Serine Proteases / metabolism
  • Signal Transduction
  • Skin / enzymology*
  • Wound Healing*

Substances

  • Fibrinolytic Agents
  • Intercellular Signaling Peptides and Proteins
  • Cysteine Proteases
  • Peptide Hydrolases
  • Serine Proteases
  • Fibrinolysin
  • Matrix Metalloproteinases