Cartilage-like composition of keloid scar extracellular matrix suggests fibroblast mis-differentiation in disease

Javier Barallobre-Barreiro, Elizabeth Woods, Rachel Emma Bell, Jennifer Anne Easton, Carl Hobbs, Michael Eager, Ferheen Baig, Alastair MacKenzie Ross, Rajeev Mallipeddi, Barry Powell, Mark Soldin, Manuel Mayr, Tanya J Shaw

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Following wound damage to the skin, the scarring spectrum is wide-ranging, from a manageable normal scar through to pathological keloids. The question remains whether these fibrotic lesions represent simply a quantitative extreme, or alternatively, whether they are qualitatively distinct. A three-way comparison of the extracellular matrix (ECM) composition of normal skin, normal scar and keloids was performed using quantitative discovery-based proteomics. This approach identified 40 proteins that were significantly altered in keloids compared to normal scars, and strikingly, 23 keloid-unique proteins. The major alterations in keloids, when functionally grouped, showed many changes in proteins involved in ECM assembly and fibrillogenesis, but also a keloid-associated loss of proteases, and a unique cartilage-like composition, which was also evident histologically. The presence of Aggrecan and Collagen II in keloids suggest greater plasticity and mis-differentiation of the constituent cells. This study characterises the ECM of both scar types to a depth previously underappreciated. This thorough molecular description of keloid lesions relative to normal scars is an essential step towards our understanding of this debilitating clinical problem, and how best to treat it.

Original languageEnglish
JournalMatrix Biology Plus
DOIs
Publication statusE-pub ahead of print - 30 Oct 2019

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