Effect of the cardiac long non-coding RNA Charme depletion on the maturation and paracrine signaling of resident cardiac fibroblasts [RNA-Seq 2]

CharmeKO CFs show impaired phenotypic conversion into myofibroblasts and reduced responsiveness to activation stimuli, accompanied by the retention of features proper of unactivated mesenchymal cells. Charme depletion also affects CF paracrine function, determining an impoverishment in cardioprotective cytokines in their secretome, with consequent reduced ability to mediate PI3K/Akt pathway activation in cardiomyocytes and to induce the angiogenic process in endothelial cells.

CharmeKO CFs also proved to be less supportive to cardiomyocyte maturation in an in vitro model of cardiac differentiation, thus indicating a potential contribution to the in vivo impairment of cardiomyocyte maturation. Overall, the evidence collected suggests that Charme depletion in the heart impacts CF maturation capacity, leading to their impaired function, which can potentially contribute to the alterations observed in the CharmeKO mice.

These findings pave the way to deeper investigations of the intercellular signalling occurring in the heart upon Charme ablation with the aim of identifying how microenvironment homeostasis contributes to cardiomyocyte maturation, and is potentially involved in cardiac diseases.