Kangfuxin Oral Liquid Attenuates Bleomycin-Induced Pulmonary Fibrosis via the TGF- β 1/Smad Pathway

TIAN²,

DU³

et al. 2020

Preprint

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.

Section: Discussionmentioning

confidence: 53%

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

TIAN²,

DU³

et al. 2020

Preprint

“…In vivo studies, we further revealed H19 de ciency signi cantly blocked bleomycin-induced pulmonary brosis and reduced the cell proliferation. TGF-β/smad signaling is one of the key pathways responsible for pulmonary brosis [31,[44][45][46]. We here showed that bleomycin induced Tgfb1 mRNA expression and activated the Smad2 and Smad3, but not in the H19 -/mice.…”

Section: Discussionmentioning

confidence: 56%

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

TIAN²,

DU³

et al. 2020

Preprint

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 pathogenesis 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 and western blot. H19 knockout (H19-/-) mice were generated by CRISPR/Cas9 and used to investigate the roles of H19 in the pulmonary inflammation and fibrosis in vivo.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 pulmonary fibrosis.

“…In vivo studies, we further revealed H19 de ciency signi cantly blocked bleomycin-induced pulmonary brosis and reduced the alveolar type II cells regeneration. TGF-β/smad signaling is one of the key pathways responsible for pulmonary brosis (31,(43)(44)(45). We here showed that bleomycin induced Tgfb1 mRNA expression and activated the Smad1/5, Smad2 and Smad3, but not in the H19-/-mice.…”

Section: Discussionmentioning

confidence: 56%

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

Tian²,

Du³

et al. 2020

Preprint

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.