Long noncoding RNA H19 controls DUSP5/ERK1/2 axis in cardiac fibroblast proliferation and fibrosis.
Down-regulation of DUSP5 has been shown to increase cell proliferation. DUSP5 expression is regulated through epigenetic events involving LncRNA H19 human choriocarcinoma cell line. However, the molecular mechanisms of H19 modulating the DUSP5 expression in cardiac fibrosis remain largely unknown. Here, we identify H19 negatively regulation of DUSP5 gene expression in cardiac fibroblast and fibrosis tissues. In vivo, the expression levels of H19, DUSP5, α-SMA, p-ERK1/2, and ERK1/2 in cardiac fibrosis tissue were estimated by Western blotting, quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. In vitro stimulation of freshly isolated rat cardiac fibroblasts with recombinant marine TGF-β1 was performed, followed by quantitative reverse transcription-polymerase chain reaction and Western blotting to detect changes in H19, DUSP5, p-ERK1/2, and ERK1/2 levels. Cardiac fibroblasts were transfected with pEX-3-H19 overexpressing, H19-RNAi down-regulating, or pEGFP-C1-DUSP5 overexpressing. Finally, cell proliferation was assessed by the MTT assay and cell cycle. H19 endogenous expression is overexpressed in cardiac fibroblast and fibrosis tissues, and an opposite pattern is observed for DUSP5. H19 ectopic overexpression reduces DUSP5 abundance and increases the proliferation of cardiac fibroblast, whereas H19 silencing causes the opposite effects. In a broader perspective, these results demonstrated that LncRNA H19 contributes to cardiac fibroblast proliferation and fibrosis, which act in part through repression of DUSP5/ERK1/2.
Department of Cardiothoracic Surgery, The Second Hospital of Anhui Medical University, Hefei 230601, China.
Hui
H
Tao
Department of Cardiothoracic Surgery, The Second Hospital of Anhui Medical University, Hefei 230601, China.
Wei
W
Cao
Department of Pharmacology, The Second Hospital of Anhui Medical University, Hefei 230601, China.
Jing-Jing
JJ
Yang
Department of Cardiothoracic Surgery, The Second Hospital of Anhui Medical University, Hefei 230601, China. Electronic address: ayskh3@hotmail.com.
Kai-Hu
KH
Shi
Department of Cardiothoracic Surgery, The Second Hospital of Anhui Medical University, Hefei 230601, China. Electronic address: 13905601531@139.com.
Xiao
X
Zhou
Department of Pharmacology, The Second Hospital of Anhui Medical University, Hefei 230601, China.
Li-Ping
LP
Liu
School of Pharmacy, Anhui Medical University, Hefei 230032, China.
Jun
J
Li
D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D004195:Disease Models, Animal; D054637:Dual-Specificity Phosphatases / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006331:Heart Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008297:Male; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D054637:Dual-Specificity Phosphatases; C514214:Dusp5 protein, rat
Cardiac fibroblasts; Cardiac fibrosis; DUSP5; H19; Long noncoding RNA; Proliferation