Targeting AnxA2-EGFR Signaling: Hydroxychloroquine As a Therapeutic Strategy for Bleomycin-induced Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a disease that causes progressive failure of lung function, and its molecular mechanism remains poorly understood. However, the AnnexinA2-epidermal growth factor receptor (EGFR) signaling pathway has been identified as playing a significant role in its development. Hydroxychloroquine, a common anti-malarial drug, has been found to inhibit this pathway and slow down the progression of IPF. To better understand the role of the AnxA2-EGFR signaling pathway in pulmonary fibrosis, an in vivo study was conducted. In this study, mice were induced with pulmonary fibrosis using bleomycin, and HCQ was administered intraperitoneally the next day of bleomycin induction. The study also employed nintedanib as a positive control. After the induction, the lungs showed increased levels of fibronectin and vimentin, along with enhanced expression of AnxA2, EGFR, and Gal-3, indicating pulmonary fibrosis. Additionally, the study also found that HCQ significantly inhibited these effects and showed antifibrotic properties similar to nintedanib. Overall, these findings suggest that HCQ can attenuate bleomycin-induced pulmonary fibrosis by inhibiting the AnxA2-EGFR signaling pathway. These results are promising for developing new treatments for IPF.