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

Alexander L Reese-Petersen; Federica Genovese; Lei Zhao; Glen Banks; David A Gordon; Morten A Karsdal

doi:10.3389/fmolb.2023.1228232

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

Front Mol Biosci. 2023 Jul 12:10:1228232. doi: 10.3389/fmolb.2023.1228232. eCollection 2023.

Authors

Alexander L Reese-Petersen¹, Federica Genovese¹, Lei Zhao², Glen Banks², David A Gordon², Morten A Karsdal¹

Affiliations

¹ Nordic Bioscience A/S, Herlev, Denmark.
² Bristol Myers Squibb, New York, NJ, United States.

Abstract

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.

Keywords: ECM; biomarkers; collagen; endotrophin; extracellular matrix; fibrosis; heart failure.