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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:21

Enthalten in:

Respiratory research - 21(2020), 1 vom: 02. Nov., Seite 290

Sprache:

Englisch

Beteiligte Personen:

Wan, Xiaoyu [VerfasserIn]
Tian, Xinbei [VerfasserIn]
Du, Jun [VerfasserIn]
Lu, Ying [VerfasserIn]
Xiao, Yongtao [VerfasserIn]

Links:

Volltext

Themen:

11056-06-7
Bleomycin
EC 2.7.1.-
H19 long non-coding RNA
Interleukin-6
Interleukin-6, mouse
Journal Article
LncRNA H19
Phosphotransferases (Alcohol Group Acceptor)
Pulmonary fibrosis
RNA, Long Noncoding
S1pr2
STAT3 Transcription Factor
Smad
Smad Proteins, Receptor-Regulated
Sphingosine kinase 2, mouse
Sphingosine-1-Phosphate Receptors
Sphingosine-1-phosphate receptor-2, mouse
Stat3 protein, mouse
Tgfb1 protein, mouse
Transforming Growth Factor beta1

Anmerkungen:

Date Completed 15.09.2021

Date Revised 15.09.2021

published: Electronic

Citation Status MEDLINE

doi:

10.1186/s12931-020-01534-6

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM317071548