Involvement of lncR-30245 in myocardial infarction-induced cardiac fibrosis through PPAR-γ-mediated CTGF signaling pathway

Background Long noncoding RNAs (lncRNAs) are emerging as important mediators of cardiac pathophysiology. The aim of the present study is to investigate the effects of an lncRNA lncR-30245 on cardiac fibrogenesis and the underlying mechanism. Methods Myocardial infarction (MI) and transforming growth factor-beta 1 (TGF-β1) were used to induce fibrotic phenotypes. Cardiac fibrosis was detected by Masson’s trichrome staining. Cardiac function was evaluated by echocardiography. Western blot, quantitative RT-PCR, and pharmacological approaches were employed to investigate the role of lncR-30245 in cardiac fibrogenesis. Results Expression of lncR-30245 was significantly increased in MI hearts and TGF-β1-treated cardiac fibroblasts (CFs). LncR-30245 was mainly located in the cytoplasm. Overexpression of lncR-30245 promoted collagen production and CFs proliferation. Knockdown of lncR-30245 significantly inhibited TGF-β1-induced collagen production and CFs proliferation. LncR-30245 overexpression inhibited the anti-fibrotic role of peroxisome proliferator-activated receptor gamma (PPAR-γ) and increased connective tissue growth factor (CTGF) expression, while lncR-30245 knockdown exerted the opposite effects. Rosiglitazone, a PPAR-γ agonist, significantly inhibited lncR-30245-induced CTGF upregulation and collagen production in CFs. In contrast, T0070907, a PPAR-γ antagonist, attenuated the inhibitory effects of lncR-30245 siRNA on TGF-β1-induced CTGF expression and collagen production. Importantly, lncR-30245 knockdown significantly enhanced ejection fraction and fractional shortening and attenuated cardiac fibrosis in MI mice. Conclusion Our study indicates that the lncR-30245/PPAR-γ/CTGF pathway mediates MI-induced cardiac fibrosis and might be a therapeutic target for various cardiac diseases associated with fibrosis.