Long non-coding RNA H19 deficiency ameliorates bleomycin-induced pulmonary inflammation and fibrosis

Xiaoyu Wan,Ying Lu,Yongtao Xiao,Xinbei Tian,Jun Du

doi:10.1186/s12931-020-01534-6

Abstract

BackgroundThe poor understanding of pathogenesis in idiopathic pulmonary fibrosis (IPF) impaired development of effective therapeutic strategies. The aim of the current study is to investigate the roles of long non-coding RNA H19 (lncRNA H19) in the pulmonary inflammation and fibrosis of IPF.MethodsBleomycin was used to induce pulmonary inflammation and fibrosis in mice. The mRNAs and proteins expression in lung tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. H19 knockout (H19−/−) mice were generated by CRISPR/Cas9.ResultsThe expression of H19 mRNA was up-regulated in fibrotic lungs patients with IPF as well as in lungs tissues that obtained from bleomycin-treated mice. H19−/− mice suppressed bleomycin-mediated pulmonary inflammation and inhibited the Il6/Stat3 signaling. H19 deficiency ameliorated bleomycin-induced pulmonary fibrosis and repressed the activation of TGF-β/Smad and S1pr2/Sphk2 in the lungs of bleomycin-treated mice.ConclusionsOur data suggests that H19 is a profibrotic lncRNA and a potential therapeutic target for IPF.

Highlights

The poor understanding of pathogenesis in idiopathic pulmonary fibrosis (IPF) impaired development of effective therapeutic strategies
H19 is up‐regulated in fibrotic lungs Analysis of publicly available datasets showed that Long non-coding RNA H19 (lncRNA) H19 expression was more highly expressed in lung tissue from patients with IPF compared to normal lung tissue, but there was no significant difference between IPF patients and other interstitial lung diseases (ILD) (Fig. 1a) [28, 29]
Fibrotic genes, including Alpha 2 smooth muscle actin (ACTA2), Collagen type I alpha 2 (COL1A2) and Matrix metalloproteinase 7 (MMP7), increasingly expressed in lung tissue from patients with IPF compared to lung tissue from patients with other ILD and to normal lung tissue (Fig. 1a) [28, 29]

Summary

Introduction

The poor understanding of pathogenesis in idiopathic pulmonary fibrosis (IPF) impaired development of effective therapeutic strategies. The aim of the current study is to investigate the roles of long non-coding RNA H19 (lncRNA H19) in the pulmonary inflammation and fibrosis of IPF. Idiopathic pulmonary fibrosis (IPF) is a progressive and highly lethal pulmonary fibrotic lung disease with poor treatment and unknown etiology, which rises significantly with age and higher in men [1,2,3,4]. LncRNAs have been shown to play important roles in different physiological activities, such as gene imprinting, cell proliferation, differentiation, apoptosis, migration, and immune responses [7, 8]. The lncRNA H19 is an imprinted and maternally expressed gene that plays a vital role in the controlling the cell proliferation and differentiation [16,17,18].

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