Aldosterone Upregulates Chemerin Via Chemokinelike Receptor 1-Rho-Rock-Jnk Signaling In Cardiac Fibroblasts

Chemerin is a novel adipokine that affects inflammation, insulin resistance, metabolic syndrome, and cardiovascular diseases. Nonetheless, it is unclear whether chemerin is expressed in cardiac fibroblasts or cardiac fibrosis, as are the effects of chemerin in this process. This study was aimed at investigating the regulation of the chemerin release and its effects on cardiac fibroblasts. Rat cardiac fibroblasts were cultured and exposed to increasing concentrations of aldosterone for 4-48 h. Y27632 was used to block ROCK signaling. PD98059, SB203580, and SP600125 were used to inhibit ERK1/2, p38 MAPK, and JNK signaling pathways, respectively. RT-PCR and western blotting were carried out to determine the expression levels of chemerin. CMKLR1, TGF-beta, ROCK1, ROCK2, MYPT1, and JNK were assayed by western blot analysis. Chemerin and CMKLR1 were expressed in cardiac fibroblasts. Aldosterone increased chemerin mRNA and protein levels in a time-and dose-dependent manner in cardiac fibrosis. Spironolactone, Y27632, and SP600125 effectively suppressed the expression of chemerin. Our study revealed that chemerin and CMKLR1 are expressed in cardiac fibroblasts and the expression levels of chemerin are increased in cardiac fibrosis. Thus, chemerin may play an important role in cardiac fibrosis. Our study showed that chemerin may play this role via molecular mechanisms mediated by the CMKLR1-Rho-ROCK1-JNK signaling pathway.