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

Abstract

Background: The limited understanding of pathogenesis in idiopathic pulmonary fibrosis (IPF) impaired development of effective therapeutic strategies.The aim of this study was to investigate the role of long non-coding RNA H19 (lncRNA H19) in the progression of IPF. Methods: Bleomycin was used to induce pulmonary fibrosis in mice. The mRNAs and proteins expression in lung tissues with bleomycin-induced pulmonary fibrosis was determined by quantitative real-time polymerase chain reaction and western blot. H19 deficiency (H19-/-) were generated by CRISPR/Cas9 and were used to investigate the roles of H19 in the pulmonary inflammation and fibrosis in vivo.Results: The expression of H19 was up-regulated in fibrotic lungs patients with IPF and mouse lungs obtained from bleomycin-treated mice. H19 deficiency reduced bleomycin-induced pulmonary inflammation and inhibited the activation of Il6/Stat3 signaling. H19 deficiency ameliorated bleomycin-induced pulmonary fibrosis and repressed the activation of TGFβ-Smad and S1pr2/Sphk2 in the lungs of bleomycin-treated mice. H19 depletion attenuated the lung regeneration and reduced expression of activated Egfr. Conclusions: Our data suggest that H19 is a profibrotic lncRNA and a potential therapeutic target for pulmonary fibrosis.

Long non‐coding RNAs: Promising new targets in pulmonary fibrosis

“…H19 downregulation alleviates fibroblast activation and lung fibrosis 77,78 . Wan et al 79 . further confirmed that H19 deficiency ameliorates bleomycin‐induced pulmonary infammation and fibrosis by using H19 knockout (H19−/−) mice generated by CRISPR/Cas9.…”