sRAGE Inhibits the Mucus Hypersecretion in a Mouse Model with Neutrophilic Asthma

ABSTRACT

Background

Neutrophilic asthma (NA) may result in irreversible airflow limitations. Soluble advanced glycosylation receptor (sRAGE) has been shown to be associated with neutrophilic airway inflammation. However, the association between sRAGE and mucus hypersecretion in NA remains unknown. This study aims to assess the function of sRAGE on mucus hypersecretion.

Methods

A NA mouse model was established and treated with adeno-associated virus 9 (AAV9)-sRAGE and inhibitors. Collagen deposition and goblet cell hyperplasia in the lungs were evaluated by periodic acid-Schiff (PAS) and Masson staining. sRAGE and mucin levels in bronchoalveolar lavage fluid were measured by ELISA. Pathway molecule expression levels were determined by RT-qPCR and western blotting.

Results

The results showed that the NA mouse model exhibited airway mucus hypersecretion. Mice can be effectively transfected by AAV9-sRAGE via tail-vein injection and intranasal drip. AAV9-sRAGE increased the sRAGE levels but it inhibited the collagen deposition, the PAS score, as well as the expression of MUC5AC and MUC5B. Inhibitors of high-mobility group protein 1 (HMGB1), receptor for advanced glycation end product (RAGE) and phosphatidylinositol 3-kinase (PI3K) suppressed the MUC5AC levels in NA mice as well as in cultured HMGB1-induced human bronchial epithelial cells. Furthermore, the phospho- extracellular signal-regulated kinase (ERK) protein in NA was increased while the sRAGE intervention inhibited this elevation.

Conclusions

These results suggest that sRAGE may be a potential target for the treatment of mucus hypersecretion in NA.

KEYWORDS:

• sRAGE
• p-ERK
• bronchial epithelial cells
• neutrophilic asthma
• mucus hypersecretion

Availability of data and material

Data are available from the corresponding author on reasonable request.

Ethics approval

All animal experiments were approved by The Ethics Committee of The First Affiliated Hospital of Guangxi Medical University [2019 (KY-E-035)].

Consent for publication

All the authors approved the publication.

Competing interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Author contribution

X.Z. performed and analyzed the experiments, conceived and wrote the manuscript; J.X., H.S and Q. W conducted the cell and animal studies; G.N. designed and supervised the study, as well as critically revised the manuscript and had the primary responsibility for writing. All authors contributed to the writing of the manuscript.

Additional information

Funding

This study was supported by International Communication of Guangxi Medical University; Innovation Project of Guangxi Graduate Education [YCBZ2019045]; Guangxi Health and Health Committee Project [Z20190762]; Chen Xiaoping foundation for the development of science and technology of Hubei province [CXPJJH1 1900003-17]; International Communication of Guangxi Medical University Graduate Education [.]; Guangxi Natural Science Foundation [2018GXNSFAA281256];