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.