Expression of the Close homolog of L-1 and embigin identifies activated myofibroblasts.
Stock, A.; Day, J.; Huckstep, H.; Garnham, A.; Wicks, I. P.
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AbstractFibrosis is driven by the emergence of myofibroblasts, which are the primary producers of the extracellular matrix proteins that form fibrotic lesions. Despite this critical role, detecting myofibroblasts remains challenging due to the paucity of selective markers. We therefore screened for novel myofibroblast-specific markers, discovering that the expression of the close homolog of L1 (ChL-1) and embigin (Emb) distinguish activated myofibroblasts from their quiescent precursors. We report that ChL-1+/Emb+ fibroblasts: (1) emerge during cardiac inflammation, (2) have elevated expression of collagens and inflammatory factors and (3) localise to fibrotic zones - consistent with activated myofibroblasts. Mechanistically, Chl1+/Emb+ myofibroblasts differentiate from resident fibroblasts which upregulate these markers in response to proinflammatory cytokines, such as IL-1 and IL-17. Moreover, we show that embigin could be exploited to target antibody-based therapies to myofibroblasts and confirm this protein as a conserved marker of activated fibroblasts in multiple tissues and settings. Collectively, these findings identify ChL-1 and embigin as novel myofibroblast surface-markers that could be used to identify, enumerate and target this pathogenic population.
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