Abstract
Background:Chemerin expression has been documented to be increased in patients with heart failure (HF), animal models of myocardial fibrosis (MF), and proliferation of cardiac fibroblasts (CFs). However, the mechanisms underlying the chemerin high-proliferation processes in CFs remain unknown. The aim of this study was to elucidate the effects and mechanisms on chemerin that promote the proliferation of CFs.
Methods : CFs were isolated from 3-day-old Sprague-Dawley (SD) rats and cultured. They were identified by immunofluorescence. Aldosterone-induced proliferation model of CFs. The role of chemerin on the proliferation of CFs were determined by EdU. PI3k/Akt/NF-κB signal transduction was inhibited by pretreatment with the PI3k/Akt/NF-κB inhibitor LY294002 and PDTC. real-time quantitative PCR（RT-qPCR）and Western blotting were used to test the expression of relevant genes.
Results:By immunofluorescence staining of vimentin, the extracted cells can be identified as CFs.
Aldosterone induces the proliferation of CFs, we found that aldosterone promoted upregulation of chemerin, CMKLR1 and PCNA expression. And then we found that CMKLR1 expression was upregulated in CFs in response to exogenous chemerin stimulation, whereas the exogenous chemerin significantly promoted the proliferation of CFs. Mechanistically, exogenous chemerin increased the phosphorylated PI3k/Akt and NF-κB levels in CFs. Alternatively, blockade of PI3k/Akt and NF-κB inhibited the promoting proliferation effects of chemerin.
Conclusions: Our study found that chemerin promoted the proliferation of CFs through upregulation of CMKLR1 receptors. We also found that chemerin promotes the proliferation of CFs via the PI3k/Akt/NF-κB signaling pathway. Chemerin is expected to be a target for therapy against myocardial fibrosis.