Exosomal transfer of activated neutrophil-derived lncRNA CRNDE promotes proliferation and migration of airway smooth muscle cells in asthma.

Abstract

Activated neutrophil-derived exosomes reportedly contribute to the proliferation of airway smooth muscle cells (ASMCs), thereby aggravating the airway wall remodeling during asthma; however, the specific mechanism remains unclear. Lipopolysaccharide (LPS)-EXO and si-CRNDE-EXO were extracted from the media of human neutrophils treated with LPS and LPS + si-CRNDE (a siRNA targets long non-coding RNA CRNDE), respectively. Human ASMCs were co-cultured with LPS-EXO or si-CRNDE-EXO, and cell viability, proliferation and migration were measured. The interplay of colorectal neoplasia differentially expressed (CRNDE), inhibitor of nuclear factor kappa B kinase subunit beta (IKKβ) and nuclear receptor subfamily 2 group C member 2 (TAK1) was explored using RNA immunoprecipitation (RIP) and Co-IP assays. A mouse model of asthma was induced using ovalbumin. CRNDE was upregulated in LPS-EXO and successfully transferred from LPS-treated neutrophils to ASMCs through exosome. Mechanically, CRNDE loaded in LPS-EXO reinforced TAK1-mediated IKKβ phosphorylation, thereby activating the nuclear factor kappa B (NF-κB) pathway. Functionally, silencing CRNDE in LPS-EXO, an IKKβ inhibitor, and an NF-κB inhibitor all removed the upregulation of cell viability, proliferation and migration induced by LPS-EXO in ASMCs. In the end, the in vivo experiment demonstrated that CRNDE knockdown in neutrophils effectively reduced the thickness of bronchial smooth muscle in a mouse model for asthma. Activated neutrophils-derived CRNDE was transferred to ASMCs through exosomes and activated the NF-κB pathway by enhancing IKKβ phosphorylation. The latter promoted the proliferation and migration of ASMCs and then contributed to airway remodeling in asthma.

• Authors: Xiao-Yu Zhang, Zhuo-Chang Chen, Nan Li, Zhi-Hua Wang, Ya-Li Guo, Cui-Jie Tian, Dong-Jun Cheng, Xue-Yi Tang, Luo-Xian Zhang
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 31 Issue 4 Pg. 638-650 (02 21 2022) ISSN: 1460-2083 [Electronic] England
• PMID: 34590683 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Lipopolysaccharides
• NF-kappa B
• RNA, Long Noncoding
• I-kappa B Kinase

Topics

• Airway Remodeling
• Animals
• Asthma (genetics)
• Cell Proliferation (genetics)
• Colorectal Neoplasms (metabolism)
• Disease Models, Animal
• Humans
• I-kappa B Kinase (genetics, metabolism)
• Lipopolysaccharides (pharmacology)
• Mice
• Myocytes, Smooth Muscle (metabolism)
• NF-kappa B (genetics, metabolism)
• Neutrophils (metabolism)
• RNA, Long Noncoding (genetics, metabolism)