1. Academic Validation
  2. Long non-coding RNA H19 deficiency ameliorates bleomycin-induced pulmonary inflammation and fibrosis

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

  • Respir Res. 2020 Nov 2;21(1):290. doi: 10.1186/s12931-020-01534-6.
Xiaoyu Wan 1 Xinbei Tian 2 Jun Du 2 Ying Lu 2 Yongtao Xiao 3 4
Affiliations

Affiliations

  • 1 Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
  • 2 Shanghai Institute for Pediatric Research, Shanghai, China.
  • 3 Shanghai Institute for Pediatric Research, Shanghai, China. xiaoyongtao@xinhuamed.com.cn.
  • 4 Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665, Kong Jiang Road, Shanghai, China. xiaoyongtao@xinhuamed.com.cn.
Abstract

Background: 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.

Methods: Bleomycin 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.

Results: The 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.

Conclusions: Our data suggests that H19 is a profibrotic lncRNA and a potential therapeutic target for IPF.

Keywords

Pulmonary fibrosis; S1pr2; Smad; lncRNA H19.

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