Long non-coding RNA H19 deficiency ameliorates bleomycin-induced pulmonary inflammation and fibrosis
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RESEARCH
Long non‑coding RNA H19 deficiency ameliorates bleomycin‑induced pulmonary inflammation and fibrosis Xiaoyu Wan1, Xinbei Tian2, Jun Du2, Ying Lu2 and Yongtao Xiao2,3*
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, lncRNA H19, Smad, S1pr2 Background 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 [1–4]. Patients with IPF present similar characteristics to the usual interstitial pneumonia (UIP), including extracellular matrix deposition, alveolar architectural disruption, and subpleural honeycombing [5]. The patients with IPF usually have clinical experiences from cough to respiratory insufficiency and have a median survival time of 3 to 5 years after diagnosis [1, 4]. Unfortunately, there are currently *Correspondence: [email protected] 3 Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665, Kong Jiang Road, Shanghai, China Full list of author information is available at the end of the article
no effective therapies capable of stabilizing or improving lung function for patients with IPF. Long non-coding RNAs (lncRNAs) are defined as nonprotein encoding RNA molecules that are more than 200 bp long in length [6]. 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]. Recent studies have shown that aberrant expression of lncRNAs are associated with a number of human diseases, including cardiovascular, neurodegenerative, lung diseases, tumors and infections [9–15]. The lncRNA H19 is an imprinted and maternally expressed gene that plays a vital role in the controlling the cell proliferation and differentiation [16–18]. The others and our recent stu
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