Blockade of pentraxin 3/CD44 interaction on attenuation and reversal of lung injury-induced fibrosis

Fibrosing interstitial lung disease (fILD) is a fatal fibrotic lung disease with limited therapeutic options and no effective therapeutic strategies to reverse pulmonary fibrosis. Here, we found that PTX3 is upregulated in the lungs of bleomycin-treated mice and fILD patients. Lung injury and fibrosis were significantly attenuated in inducible conditional Ptx3-deficient mice in response to bleomycin treatment. Moreover, we dissected mechanistic insights into PTX3/CD44-dependent fibrotic pathways and effectors in lung myofibroblast activation and collagen production. Importantly, αPTX3i disrupts the interaction of PTX3 and CD44 and effectively attenuated bleomycin-treated lung injury and fibrosis in vivo and myofibroblast activation in vitro. Our study provides new insight into the regulation of PTX3 in pulmonary fibrosis and a potential target for developing future novel therapy for fILDs. C57BL/6 mice were exposed to either saline or bleomycin (2 mg/kg) via intratracheal instillation. Administration of αPTX3i (10 mg/kg) or IgG1κ (10 mg/kg) was performed on days 14 and 21 after bleomycin administration by intraperitoneal injection. At day 28, the lungs were harvested, total RNA was extracted and subjected to RNA-sequencing.