Open Access
ARTICLE
FBXW7 regulates epithelial barrier impairment in human bronchial epithelial cells in vitro by targeting apoptosis signal-regulating kinase1 via the p38 pathway
JINGRONG SONG#, JUAN KANG#, WEI LV, YAN DONG, XIAOYING ZHANG*
Department of Pediatrics, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China
* Address correspondence to: XiaoYing Zhang,
# These authors contributed equally to this work
BIOCELL 2021, 45(3), 723-731. https://doi.org/10.32604/biocell.2021.014453
Received 28 September 2020; Accepted 21 December 2020; Issue published 03 March 2021
Abstract
Bronchial asthma is a common chronic inflammatory disease characterized by airway hyperresponsiveness (AHR),
inflammatory cell infiltration, and airway remodeling. F-box/WD repeat-containing protein 7 (FBXW7), an E3 ubiquitin
ligase, is required for various endothelial functions, such as cell migration, inflammation, and endothelial integrity. This
study aimed to investigate the role of FBXW7 in lipopolysaccharide (LPS)-induced epithelial barrier impairment in
bronchial epithelial cells in vitro. By using lentivirus-based technology, FBXW7 was overexpressed or silenced (24 h) in
human bronchial epithelial (16HBE) cells, which were treated with LPS or not (24 h). Immunoprecipitation (IP) detection
and Western blot analysis were used to evaluate the interaction of target proteins. Cell permeability was measured using
transepithelial electrical resistance and FITC dextran flux (48 h). IL-1β, IL-18 and TNF-α in cell supernatants were
measured using ELISA (48 h). The results showed that LPS stimulation suppressed FBXW7 expression in a time- and
dose-dependent manner. LPS exposure decreased cell proliferation, elevated IL-1β, IL-18 and TNF-α, increased epithelial
permeability, and p38 phosphorylation. These LPS-induced changes were partly compromised by FBXW7 overexpression.
Similar to LPS stimulation, FBXW7 knockdown increased epithelial permeability and levels of inflammatory cytokines and
p38 phosphorylation, which were, in part, blocked by apoptosis signal-regulating kinase (ASK) 1 knockdown or p38
pathway inhibition. IP and Western blot analysis showed that FBXW7 interacted with ASK1. ASK1 expression was
inversely associated with FBXW7 expression. FBXW7 overexpression markedly enhanced ASK1 ubiquitination. These data
revealed that FBXW7 counter against inflammation and protects epithelial barrier integrity in bronchial epithelial cells by
promoting ubiquitination-mediated degradation of ASK1 via the p38 pathway.
Keywords
Cite This Article
APA Style
SONG, J., KANG, J., LV, W., DONG, Y., ZHANG, X. (2021). FBXW7 regulates epithelial barrier impairment in human bronchial epithelial cells <i>in vitro</i> by targeting apoptosis signal-regulating kinase1 via the p38 pathway. BIOCELL, 45(3), 723-731. https://doi.org/10.32604/biocell.2021.014453
Vancouver Style
SONG J, KANG J, LV W, DONG Y, ZHANG X. FBXW7 regulates epithelial barrier impairment in human bronchial epithelial cells <i>in vitro</i> by targeting apoptosis signal-regulating kinase1 via the p38 pathway. BIOCELL . 2021;45(3):723-731 https://doi.org/10.32604/biocell.2021.014453
IEEE Style
J. SONG, J. KANG, W. LV, Y. DONG, and X. ZHANG "FBXW7 regulates epithelial barrier impairment in human bronchial epithelial cells <i>in vitro</i> by targeting apoptosis signal-regulating kinase1 via the p38 pathway," BIOCELL , vol. 45, no. 3, pp. 723-731. 2021. https://doi.org/10.32604/biocell.2021.014453