MiR-135a inhibits airway inflammatory response in asthmatic mice via regulating JAK/STAT signaling pathway.

Xue-Peng Huang,Cheng-Yu Qin,Yue-Ming Gao

doi:10.1590/1414-431x202010023

Abstract

The objective of this study was to investigate the inhibitory effect of miR-135a in regulating JAK/STAT signaling pathway on airway inflammation in asthmatic mice. An asthma model was established by sensitization and stimulation with ovalbumin (OVA), and the corresponding drug intervention was given from the day of stimulation by means of nasal drops. Airway hyperresponsiveness was tested. The content of miR-135a in the lung tissue of mice was detected by RT-PCR. The pathological changes of lung tissue were evaluated by HE staining. Tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-5, and eotaxin in bronchoalveolar lavage fluid (BALF) and lung tissue were detected by ELISA and immunohistochemistry, respectively. The expression of JAK/STAT signaling pathway-related protein in lung tissue was detected by western blot. To further validate the effect of miR-135a overexpression on the JAK/STAT signaling pathway, pathway activators and inhibitors were added. Compared with the OVA group, the airway hyperresponsiveness of the mice was significantly decreased after treatment with the miR-135a agonist. The expression of miR-135a was significantly increased in the lung tissue and the pathological changes of the lung tissue were alleviated. The contents of TNF-α, IL-6, IL-5, and eotaxin in BALF and lung tissues were decreased. The expression of JAK/STAT signaling pathway-related proteins p-JAK3/JAK3, p-STAT1/STAT1, and p-STAT3/STAT3 were significantly reduced in lung tissue (P<0.05). Addition of JAK inhibitor AG490 reduced airway inflammation in asthmatic mice. miR-135a agonists inhibit airway inflammation in asthmatic mice by regulating the JAK/STAT signaling pathway.

Highlights

Asthma is a complex inflammatory disease that is prone to long-term recurrence
Data are reported as means±SD. *Po0.05 compared to the control group; #Po0.05 compared to the ovalbumin (OVA) group (ANOVA)
Data are reported as means±SD. *Po0.05 compared to the control group; #Po0.05 compared to the ovalbumin (OVA) group; ̂ Po0.05 compared to the miR-135a (ANOVA)

Summary

Introduction

Asthma is a complex inflammatory disease that is prone to long-term recurrence. It affects about 3 million people worldwide from infants to old age, and can cause 0.250–0.345 million deaths per year [1,2]. The main pathological changes are the disorder of overall and local immune inflammatory responses, especially the non-specific airway inflammation mainly caused by eosinophils, mast cells, and their secreted inflammatory mediators and cytokines [9,10]. Common asthma phenotypes include inflammatory phenotypes, clinical phenotypes, age-related phenotypes, trigger phenotypes, therapeutic response phenotypes, and obesity-related phenotypes [12]. The pathogenesis of asthma can be summarized as the result of airway immune inflammatory mechanisms, neuromodulation mechanisms, and the interaction of polygenic inheritance and environment [13]. The main treatment methods are traditional medicine, targeted therapy, and interventional therapy [15]

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Conclusion