Cell–matrix interactions governing skin repair: matricellular proteins as diverse modulators of cell function

Cell–matrix interactions governing skin repair: matricellular proteins as diverse modulators of cell function John T Walker,1,* Shawna S Kim,1,* Sarah Michelsons,1,* Kendal Creber,2,* Christopher G Elliott,1,* Andrew Leask,3 Douglas W Hamilton1–3 1Department of Anatomy and Cell Biology, 2Graduate Program of Biomedical Engineering, 3Division of Oral Biology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada *These authors contributed equally to this paper Abstract: With the classification first proposed by the Bornstein group in 1995, matricellular proteins represent a diverse and expanding class of molecules that contribute to cell phenotype and regulate interactions with the extracellular matrix. Based on initial analysis, matricellular protein expression was thought to be limited to development, but in the intervening 20 years it has become apparent that it plays a pivotal role during healing in several different tissue types. Furthermore, while considered to modulate cell behavior, it is now apparent that matricellular proteins also function in the organization and crosslinking of the extracellular matrix during healing. The focus of this review is to discuss matricellular proteins in the context of skin healing, which in healthy individuals occurs through four overlapping temporal phases. We will also discuss matricellular proteins as potential therapeutics for the treatment of impaired skin healing.