The long non-coding RNA PFI protects against pulmonary fibrosis by interacting with splicing regulator SRSF1

2021 ◽  
Author(s):  
Jian Sun ◽  
Tongzhu Jin ◽  
Wei Su ◽  
Yingying Guo ◽  
Zhihui Niu ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Non Coding Rna ◽  
Splicing Regulator ◽  
Long Non Coding Rna

scholarly journals Targeting the DNM3OS / miR-199a~214 cluster for the treatment of fibroproliferative diseases

2018 ◽  
Author(s):  
G. Savary ◽  
M. Buscot ◽  
E. Dewaeles ◽  
S. Diazzi ◽  
N. Nottet ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Mature Mirnas ◽  
Kidney Fibrosis ◽  
Downstream Effector ◽  
Non Coding Rna ◽  
Fibrotic Diseases ◽  
Fibrotic Disorders ◽  
Long Non Coding Rna ◽  
Lung And Kidney

AbstractGiven the paucity of effective treatments for fibrotic disorders, new insights into the deleterious mechanisms controlling fibroblast activation, the key cell type driving the fibrogenic process, are essential to develop new therapeutic strategies. Here, we identified the long non-coding RNA DNM3OS as a critical downstream effector of TGF-β-induced myofibroblast activation. Mechanistically, DNM3OS regulates this process in trans by giving rise to 3 distinct profibrotic mature miRNAs (i.e. miR-199a-5p/3p and miR-214-3p), which influence both SMAD and non-SMAD components of TGF-β signaling in a multifaceted way, through two modes of action consisting of either signal amplification or mediation. Finally, we provide preclinical evidence that interfering with DNM3OS function using distinct strategies not only prevents lung and kidney fibrosis but also improves established lung fibrosis, providing thus a novel paradigm for the treatment of refractory fibrotic diseases such as idiopathic pulmonary fibrosis.One Sentence SummaryThe DNM3OS lncRNA is a reservoir of fibromiRs with major functions in fibroblast response to TGF-β and represents a valuable therapeutic target for refractory fibrotic diseases such as idiopathic pulmonary fibrosis (IPF).

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

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoyu Wan ◽  
Xinbei Tian ◽  
Jun Du ◽  
Ying Lu ◽  
Yongtao Xiao
Keyword(s):  
Pulmonary Fibrosis ◽  
Pulmonary Inflammation ◽  
Chain Reaction ◽  
Potential Therapeutic Target ◽  
Qrt Pcr ◽  
Stat3 Signaling ◽  
Non Coding Rna ◽  
Poor Understanding ◽  
Polymerase Chain ◽  
Long Non Coding Rna

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.

scholarly journals Profiling long non-coding RNA changes in silica-induced pulmonary fibrosis in rat

2019 ◽  
Vol 310 ◽  
pp. 7-13 ◽  
Author(s):  
Linlin Sai ◽  
Gongchang Yu ◽  
Cunxiang Bo ◽  
Yu Zhang ◽  
Zhongjun Du ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Non Coding Rna ◽  
Long Non Coding Rna

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

2020 ◽  
Author(s):  
XIAOYU WAN ◽  
XINBEI TIAN ◽  
JUN DU ◽  
YING LU ◽  
YONGTAO XIAO
Keyword(s):  
Pulmonary Fibrosis ◽  
Pulmonary Inflammation ◽  
Chain Reaction ◽  
Potential Therapeutic Target ◽  
Qrt Pcr ◽  
Stat3 Signaling ◽  
Non Coding Rna ◽  
Poor Understanding ◽  
Polymerase Chain ◽  
Long Non Coding Rna

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 pulmonary fibrosis.

scholarly journals Telomeric repeat-containing ribonucleic acid (TERRA) expression in patients with idiopathic pulmonary fibrosis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Manal M. El-Desoky ◽  
Asem A. Hewidy ◽  
Ahmed M. Fouda ◽  
Fatma Azzahraa Hisham
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Telomeric Repeat ◽  
Expression Level ◽  
Strongly Correlated ◽  
High Resolution Computed Tomography ◽  
Non Invasive ◽  
Non Coding Rna ◽  
Extent Score ◽  
Long Non Coding Rna

Abstract Background Idiopathic pulmonary fibrosis (IPF) represents a chronic disease with a progressive course. It is characterized by excessive lung scarring that ultimately contributes to irreversible lung function reduction. Interestingly, a type of long non-coding RNA termed as telomeric repeat-containing RNA (TERRA) is linked to fibrosis pathophysiology, including IPF. In this study, the expression profile of TERRA was investigated in IPF patients on radiological diagnosis [unusual interstitial pattern (UIP) in high-resolution computed tomography (HRCT)] to evaluate whether it could be employed as a reliable diagnostic biomarker. Results TERRA expression level was significantly higher in IPF patients over healthy controls. The expression level was significantly inversely correlated with the percentage of forced vital capacity predicted (FVC% predicted). By contrast, it was significantly directly correlated with HRCT reticular extent score. Conclusion TERRA expression is an essential biomarker in peripheral blood of IPF patients, providing a valuable non-invasive tool for IPF diagnosis. Moreover, TERRA expression is strongly correlated with UIP in HRCT reticular extent score.

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