Elevated PRELP expression in heart and liver fibrosis promotes collagen production

Abstract

Fibrosis results from the excessive production of extracellular matrix proteins by myofibroblasts. It has recently been reported that in the heart, myofibroblasts develop chondrocyte-like properties following myocardial infarction as fibrosis progresses and tissues stiffen. However, the nature of these chondrocyte-like myofibroblasts remains unclear. In this study, we found that the expression of the proline- and arginine-rich end leucine-rich repeat protein (PRELP) was upregulated in hearts and livers stiffened by fibrosis with chronic inflammation. Moreover, we established that Prelp was specifically expressed in chondrocyte-like myofibroblasts. Prelp expression was found to be regulated by the transcription factor SOX9, and in cardiac and liver myofibroblasts, Prelp-knockdown was observed to reduce collagen expression. These findings reveal that PRELP is specifically expressed in chondrocyte-like myofibroblasts and that it promotes collagen production. PRELP could thus serve as a novel therapeutic target for treating fibrosis.

Keywords: Fibrosis; MASH; Myocardial infarction; Myofibroblast; PRELP.