TIM-1 attenuates airway mucus hypersecretion and inflammation induced by cigarette smoke via the PI3K/Akt signaling pathway.

Abstract

Cigarette smoke extract (CSE)-induced airway mucus hypersecretion and inflammation are prominent features of chronic obstructive pulmonary disease (COPD). As a factor associated with inflammation regulation, T cell immunoglobulin and mucin domain-1 (TIM-1) is found to be involved in various inflammatory disorders such as asthma and COPD. In this study, the GEO database provides two human COPD gene expression datasets (GSE67472, n = 62) along with the relevant controls (n = 43) for differentially expressed gene (DEG) analyses. Candidate biomarkers are identified, and the discriminatory ability is determined using the area under the receiver operating characteristic curve (AUC) values. Furthermore, a COPD mouse model is established using CSE to validate that anti-TIM-1 can attenuate airway mucus hypersecretion and inflammation via the PI3K/Akt signaling pathway in COPD. Anti-TIM-1 antibody pretreatment significantly suppresses mucin secretion, inflammatory cell infiltration, and inflammatory cytokine release in mouse lungs induced by CSE and also suppresses CSE-induced expression of MUC5AC. Western blot shows that the anti-TIM-1 antibody attenuates the activation of p-Akt in airway mucus hypersecretion mice induced by CSE. This study highlights the protective effect of the TIM-1 antibody on CSE-related airway mucus hypersecretion and inflammation, in which PI3K/AKT may be involved. These findings suggest that TIM-1 could be a potential therapeutic target for airway mucus hypersecretion.