Int J Biol Sci 2022; 18(1):349-359. doi:10.7150/ijbs.66215 This issue

Research Paper

ITGB4 deficiency induces mucus hypersecretion by upregulating MUC5AC in RSV-infected airway epithelial cells

Xizi Du1#, Yu Yang1#, Ming Yang2, Lin Yuan1, Leyuan Wang1, Mengping Wu1, Kai Zhou1, Wenkai Li3, Yang Xiang1, Xiangping Qu1, Huijun Liu1, Xiaoqun Qin1, Chi Liu1,4✉

1. Department of Physiology, School of Basic Medicine Science, Central South University, Changsha, Hunan, China
2. Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute, Callaghan, New South Wales, Australia
3. Department of Pediatrics, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China
4. Research Center of China-Africa Infectious Diseases, Xiangya School of Medicine Central South University, Changsha, Hunan, China
#Contributed equally.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Du X, Yang Y, Yang M, Yuan L, Wang L, Wu M, Zhou K, Li W, Xiang Y, Qu X, Liu H, Qin X, Liu C. ITGB4 deficiency induces mucus hypersecretion by upregulating MUC5AC in RSV-infected airway epithelial cells. Int J Biol Sci 2022; 18(1):349-359. doi:10.7150/ijbs.66215. Available from https://www.ijbs.com/v18p0349.htm

File import instruction

Abstract

Graphic abstract

Respiratory syncytial virus (RSV) infection is the main cause of bronchiolitis in children. Excessive mucus secretion is one of the primary symbols in RSV related lower respiratory tract infections (RSV-related LRTI), which is closely associated with the occurrence and development of asthma in later life. Integrin β4 (ITGB4) is down-regulated in the airway epithelial cells (AECs) of asthma patients which plays a critical role in the pathogenesis of asthma. However, whether ITGB4 is involved in the pathological processes of RSV infection remains unclear. In this study, we found that decreased expression of ITGB4 was negatively correlated with the level of MUC5AC in childhood AECs following RSV infection. Moreover, ITGB4 deficiency led to mucus hypersecretion and MUC5AC overexpression in the small airway of RSV-infected mice. MUC5AC expression was upregulated by ITGB4 in HBE cells through EGFR, ERK and c-Jun pathways. EGFR inhibitors treatment inhibited mucus hypersecretion and MUC5AC overexpression in ITGB4-deficient mice after RSV infection. Together, these results demonstrated that epithelial ITGB4 deficiency induces mucus hypersecretion by upregulating the expression of MUC5AC through EGFR/ERK/c-Jun pathway, which further associated with RSV-related LRTI.

Keywords: respiratory syncytial virus, MUC5AC, ITGB4, airway epithelial cell