Endotrophin, a fibroblast matrikine, may be a driver of fibroblast activation in fibro-inflammatory diseases

Extracellular matrix proteins harbor signaling domains that once released from the parent molecule can trigger cellular responses. One of these molecules is endotrophin, a type VI collagen derived fragment, whose circulatory levels have been associated to an increased risk of adverse outcome in hear...

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Bibliographic Details
Published in:Frontiers in molecular biosciences 2023-07, Vol.10, p.1228232
Main Authors: Reese-Petersen, Alexander L, Genovese, Federica, Zhao, Lei, Banks, Glen, Gordon, David A, Karsdal, Morten A
Format: Article
Language:English
Subjects:
biomarkers
collagen
ECM
extracellular matrix
fibrosis
heart failure
Molecular Biosciences
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Summary:Extracellular matrix proteins harbor signaling domains that once released from the parent molecule can trigger cellular responses. One of these molecules is endotrophin, a type VI collagen derived fragment, whose circulatory levels have been associated to an increased risk of adverse outcome in heart failure with preserved ejection fraction (HFpEF). Here we show that the stimulation of human cardiac fibroblasts by endotrophin upregulates the synthesis of type I collagen, the main interstitial collagen that accumulates in the myocardium during fibrogenesis. These data provide a possible mechanistic explanation for the relation between circulating endotrophin levels and risk of outcome in HFpEF.
ISSN:2296-889X
2296-889X
DOI:10.3389/fmolb.2023.1228232