1. Involvement of lncR-30245 in Myocardial Infarction–Induced Cardiac Fibrosis Through Peroxisome Proliferator-Activated Receptor-γ–Mediated Connective Tissue Growth Factor Signalling Pathway
- Author
-
Tingting Li, Wanqi Yang, Danyang Li, Zhenwei Pan, Yuting Zhuang, Ti Yang, Qihe Huang, Hao Wu, Zhuoyun Li, Linfeng Zhan, Guiye Zhang, Yanjie Lu, and Yanan Zhuang
- Subjects
Cardiac function curve ,Heart Diseases ,Pyridines ,Cardiac fibrosis ,medicine.medical_treatment ,Myocardial Infarction ,Connective tissue ,030204 cardiovascular system & hematology ,Rosiglitazone ,Transforming Growth Factor beta1 ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,medicine ,Animals ,030212 general & internal medicine ,Cell Proliferation ,Gene knockdown ,business.industry ,Growth factor ,Connective Tissue Growth Factor ,Stroke Volume ,Fibroblasts ,medicine.disease ,Up-Regulation ,Mice, Inbred C57BL ,PPAR gamma ,CTGF ,medicine.anatomical_structure ,Benzamides ,Models, Animal ,Cancer research ,RNA, Long Noncoding ,Collagen ,Cardiology and Cardiovascular Medicine ,business ,Transforming growth factor - Abstract
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 lncR-30245, an lncRNA, on cardiac fibrogenesis and the underlying mechanism. Methods Myocardial infarction (MI) and transforming growth factor (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 reverse transcription-polymerase chain reaction, and pharmacological approaches were used 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 CF proliferation. Knockdown of lncR-30245 significantly inhibited TGF-β1–induced collagen production and CF proliferation. LncR-30245 overexpression inhibited the antifibrotic role of peroxisome proliferator-activated receptor (PPAR)-γ and increased connective tissue growth factor (CTGF) expression, whereas 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 small interfering RNA (siRNA) on TGF-β1–induced CTGF expression and collagen production. 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.
- Published
- 2019
- Full Text
- View/download PDF