Auricularia auricula polysaccharides alleviate experimental silicosis by targeting EGFR through the "gut-lung axis"

Silicosis is a major public health problem and remains a challenge for clinicians. There is an urgent need to find new drugs to minimize disease progression and deterioration. Auricularia auricula-juade is a traditional folk medicine that is used for nourishing lung functions. The aim of this study is to investigate the pharmacological action and potential mechanism of polysaccharides in Auricularia auricula for silicosis treatment. The results indicated that the Auricularia auricula polysaccharide (AAP) effectively improved silicosis induced by silica (SiO₂) in mice. The preliminary screening of differentially expressed proteins (DEPs) in the lung and intestinal tissues after AAP intervention was performed using tandem mass tag (TMT) quantitative proteomics. A common differential protein of the intestine and lungs, i.e., epidermal growth factor receptor (EGFR), was focused on using a combination of current proteomics data and a network disease database. After further validation, the use of an intestinal-lung co-culture model confirmed that AAP had the ability to attenuate the secretion of EGFR ligands (i.e., TGF-α, EGF and AREG) and modulate signaling between the intestine and lungs. This effectively inhibited the EGFR/JNK signaling pathway in lung tissues, thereby achieving therapeutic efficacy against silicosis. This study provides a solid experimental foundation of the use of AAP for silicosis treatment.