Inhibition of prostaglandin E2 receptor 4 by lnc000908 to promote the endothelial‐mesenchymal transition participation in cardiac remodelling

Autor: Jie Hu, Hao Zhou, Tiancheng Dong, Wenhua Ge, Hui Yao, Bin Geng, Lingzhi Chen, Xingxing Chen
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Cardiac function curve
Male
Epithelial-Mesenchymal Transition
Cardiac fibrosis
Prostaglandin E2 receptor
cardiac fibrosis
Regulator
Rats
Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
endothelial‐mesenchymal transition
In vivo
Transforming Growth Factor beta
Gene silencing
Medicine
Animals
Cells
Cultured
Gene knockdown
long non‐coding RNAs
Ventricular Remodeling
business.industry
Mesenchymal stem cell
Endothelial Cells
Heart
Cell Biology
Original Articles
prostaglandin E2 receptor 4
medicine.disease
Fibrosis
Rats
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
cardiovascular system
Molecular Medicine
lipids (amino acids
peptides
and proteins)
Original Article
RNA
Long Noncoding
Endothelium
Vascular
business
Receptors
Prostaglandin E
EP4 Subtype
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
1582-1838
Popis: Long non‐coding RNAs (lncRNAs) have emerged as potent regulators of cardiac disease; however, the role of lncRNA in cardiac fibrosis remains partially understood. In this study, we identified a cardiac endothelial‐enriched lncRNA‐lnc000908, which was markedly up‐regulated in rats with cardiac fibrosis. In addition, the expression of prostaglandin E2 receptor 4 (EP4) was decreased in cardiac fibrosis. In vivo lnc000908 silencing by lentivirus increased the EP4 level, decreased endothelial‐mesenchymal transition (EndMT) and improved cardiac fibrosis and cardiac function. Consistently, the lnc000908 knockdown also up‐regulated EP4 and suppressed transforming growth factor‐beta (TGF‐β)‐induced EndMT in cardiac microvascular endothelial cells. In contrast, the lnc000908 overexpression by lentivirus decreased the EP4 level and induced EndMT. Of note, these pro‐ or anti‐EndMT effects were reversed by the EP4 overexpression or the EP4 antagonist AH‐23848, respectively. This study demonstrates that lnc000908 is a novel regulator of cardiac fibrosis by modulating the EP4 expression and EndMT.
Databáze: OpenAIRE
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