Open AccessInhibition of prostaglandin E2 receptor 4 by lnc000908 to promote the endothelial‐mesenchymal transition participation in cardiac remodelling
Author(s) -
Chen Xingxing,
Ge Wenhua,
Hu Jie,
Dong Tiancheng,
Yao Hui,
Chen Lingzhi,
Geng Bin,
Zhou Hao
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14524
Subject(s) - cardiac fibrosis , gene knockdown , mesenchymal stem cell , fibrosis , cardiac function curve , regulator , gene silencing , receptor , in vivo , transforming growth factor , downregulation and upregulation , cancer research , prostaglandin e2 , biology , endocrinology , microbiology and biotechnology , medicine , heart failure , biochemistry , apoptosis , gene
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.