circELP2 reverse-splicing biogenesis and function as a pro-fibrogenic factor by targeting mitochondrial quality control pathway.

YAP1/TAZ circRNA miRNA mitochondrial quality control pathway pulmonary fibrosis

Journal

Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777

Informations de publication

Date de publication:
30 Dec 2023
Historique:
revised: 14 11 2023
received: 08 08 2023
accepted: 11 12 2023
medline: 2 1 2024
pubmed: 2 1 2024
entrez: 30 12 2023
Statut: aheadofprint

Résumé

Idiopathic pulmonary fibrosis (IPF) is considered as a chronic, fibrosing interstitial pneumonia with unknown mechanism. The present work aimed to explore the function, biogenesis and regulatory mechanism of circELP2 in pulmonary fibrosis and evaluate the value of blocking circELP2-medicated signal pathway for IPF treatment. The results showed that heterogeneous nuclear ribonucleoprotein L initiated reverse splicing of circELP2 resulting in the increase of circELP2 generation. The biogenetic circELP2 activated the abnormal proliferation and migration of fibroblast and extracellular matrix deposition to promote pulmonary fibrogenesis. Mechanistic studies demonstrated that cytoplasmic circELP2 sponged miR-630 to increase transcriptional co-activators Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ). Then, YAP1/TAZ bound to the promoter regions of their target genes, such as mTOR, Raptor and mLST8, which in turn activated or inhibited the genes expression in mitochondrial quality control pathway. Finally, the overexpressed circELP2 and miR-630 mimic were packaged into adenovirus vector for spraying into the mice lung to evaluate therapeutic effect of blocking circELP2-miR-630-YAP1/TAZ-mitochondrial quality control pathway in vivo. In conclusion, blocking circELP2-medicated pathway can alleviate pulmonary fibrosis, and circELP2 may be a potential target to treat lung fibrosis.

Identifiants

pubmed: 38159063
doi: 10.1111/jcmm.18098
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : National Natural Science Foundation of China
ID : 82370094
Organisme : National Natural Science Foundation of China
ID : 82370079
Organisme : National Natural Science Foundation of China
ID : 81870001
Organisme : National Natural Science Foundation of China
ID : 81970064
Organisme : National Natural Science Foundation of China
ID : 82170085
Organisme : Natural Science Foundation of Shandong Province
ID : ZR2020MH009
Organisme : Natural Science Foundation of Shandong Province
ID : ZR2020MH010

Informations de copyright

© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

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Auteurs

Songzi Zhang (S)

Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, China.
Department of Cellular and Genetic Medicine, Binzhou Medical University, Yantai, China.

Diwei Tu (D)

Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, China.

Weili Liu (W)

Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, China.

Ruiqiong Li (R)

Department of Clinical Nursing, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, China.

Mengqi Jiang (M)

Department of Cellular and Genetic Medicine, Binzhou Medical University, Yantai, China.

Xinglong Yuan (X)

Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, China.

Jianlin Luan (J)

Department of Cellular and Genetic Medicine, Binzhou Medical University, Yantai, China.

Hongbo Li (H)

Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, China.

Changjun Lv (C)

Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, China.

Xiaodong Song (X)

Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, China.
Department of Cellular and Genetic Medicine, Binzhou Medical University, Yantai, China.

Classifications MeSH