Open AccessRegulatory Effects of Nur77 on Airway Remodeling and ASMC Proliferation in House Dust Mite-Induced Asthma
Author(s) -
Kun Wang,
Muyun Wang,
Yan Shang,
Yide He,
Qiang Li,
Wei Gao,
Huiming Yin
Publication year - 2020
Publication title -
oxidative medicine and cellular longevity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.494
H-Index - 93
eISSN - 1942-0900
pISSN - 1942-0994
DOI - 10.1155/2020/4565246
Subject(s) - nerve growth factor ib , downregulation and upregulation , inflammation , immunology , small hairpin rna , medicine , cancer research , protein kinase b , transcription factor , biology , microbiology and biotechnology , signal transduction , apoptosis , nuclear receptor , biochemistry , gene knockdown , gene
Airway remodeling played a vital role in the development of asthma, and airway smooth muscle (ASM) mass was its hallmark. However, few strategies targeting ASM remodeling were developed in treating asthma. Nur77 was the transcription factor nuclear receptor involved in the pathogenesis of several lung diseases. Nur77 distribution and expression were determined in an HDM-mediated allergic asthma model. Its effect on airway hyperresponsiveness (AHR), chronic inflammation, and ASM remodeling in asthmatic mice was evaluated using a lentivirus-mediated shRNA. Possible mechanisms were explored by examining Nur77 actions and its underlying pathways in primary human AMC cells (ASMCs). In this study, we reported that Nur77 expression was mainly distributed along ASM and increased in lungs of HDM-challenged mice. Nur77 depletion by lentivirus-mediated shRNA ameliorated AHR, chronic inflammation, goblet cell hyperplasia, and airway remodeling in the asthmatic mouse model. By means of primary human ASMC, we discovered that Nur77 upregulation by HDM stimulation promoted cell proliferation and ROS production, as well as reduced antioxidant gene expression. These alterations might associate with MFN2/MAPK/AKT pathways. These findings broadened our understanding of airway remodeling and ASMC proliferation, which might provide a novel therapeutic target for asthma patients.