# Fyn kinase mediates the development of rats with chronic obstructive pulmonary disease by modulating the activation of p38 MAPK and NF-κB

## TL;DR

This study shows that Fyn kinase contributes to COPD development in rats by activating p38 MAPK and NF-κB pathways, suggesting it could be a potential treatment target.

## Contribution

The study identifies Fyn kinase as a novel mediator of COPD progression through specific signaling pathways.

## Key findings

- Fyn inhibition improved lung function and reduced COPD pathology in rats.
- Fyn inhibition decreased inflammatory markers like TNF-α and IL-6 in both in vivo and in vitro models.
- Fyn suppression reduced phosphorylation of p38 MAPK and NF-κB, key drivers of inflammation.

## Abstract

The current research was conducted to study the function of Fyn in a rat model of chronic obstructive pulmonary disease (COPD).

COPD in rats was induced by intratracheal instillation of lipopolysaccharide and long-term exposure to cigarette smoke. Subsequently, the rats were treated with the Fyn-specific inhibitor AZD0530. Pulmonary function, pathological appearance, and inflammatory factors were assessed in rats with COPD.

AZD0530 significantly ameliorated pulmonary function and improved the pathological manifestations of COPD in rats. AZD0530 decreased MCP-1 and CD68 expression in lung tissues, reduced inflammatory cell accumulation, and decreased TNF-α and IL-6 production in bronchoalveolar lavage fluid. In an in vitro study, pharmacological inhibition of Fyn or knockdown of Fyn by siRNA inhibited lipopolysaccharide- and cigarette smoke extract-induced TNF-α and IL-6 secretion in the human bronchial epithelial cell line BEAS-2B. Furthermore, inhibition of Fyn by either the inhibitor or siRNA Fyn reduced the phosphorylation of p38 MAPK- and NF-κB-related molecules, which strongly affected the occurrence of inflammatory responses.

Collectively, these data show that Fyn promotes COPD development by modulating the p38 MAPK and NF-κB signaling pathways. Fyn might be a promising therapeutic target for COPD.