长非编码 RNA H19 缺失可改善博来霉素诱导的肺炎症和纤维化。
Long non-coding RNA H19 deficiency ameliorates bleomycin-induced pulmonary inflammation and fibrosis.
机构信息
Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Shanghai Institute for Pediatric Research, Shanghai, China.
出版信息
Respir Res. 2020 Nov 2;21(1):290. doi: 10.1186/s12931-020-01534-6.
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.
背景
特发性肺纤维化（IPF）发病机制认识不足，阻碍了有效治疗策略的发展。本研究旨在探讨长链非编码 RNA H19（lncRNA H19）在 IPF 的肺炎症和纤维化中的作用。
方法
采用博来霉素诱导小鼠肺炎症和纤维化。通过实时定量聚合酶链反应（qRT-PCR）和 Western blot 检测肺组织中 mRNAs 和蛋白质的表达。通过 CRISPR/Cas9 生成 H19 敲除（H19）小鼠。
结果
IPF 患者纤维化肺组织以及博来霉素处理的小鼠肺组织中 H19 mRNA 表达上调。H19 小鼠抑制博来霉素介导的肺炎症，并抑制 Il6/Stat3 信号通路。H19 缺乏可改善博来霉素诱导的肺纤维化，并抑制博来霉素处理小鼠肺中 TGF-β/Smad 和 S1pr2/Sphk2 的激活。
结论
我们的数据表明，H19 是一种促纤维化 lncRNA，可能是 IPF 的治疗靶点。
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