Neutralization of the PTX3 / CD44 axis suppresses TGF ‐β1 signaling in kidney fibrosis

Renal fibrosis is a hallmark of chronic kidney disease (CKD), but effective antifibrotic therapies are lacking. Pentraxin 3 (PTX3) is markedly upregulated in CKD patients and in a unilateral ureteral obstruction (UUO) model, correlating with renal injury, extracellular matrix accumulation, partial epithelial–mesenchymal transition markers, and TGF‐β1 signaling. Genetic deletion of Ptx3 significantly attenuates UUO‐induced fibrosis. Mechanistically, PTX3 promotes transcription of LTBP‐1 and fibronectin, facilitating latent TGF‐β1 activation and inducing a profibrotic partial EMT program in tubular epithelial cells without lineage conversion. Importantly, blockade of the PTX3/CD44 axis using a neutralizing αPTX3 antibody reduced serum creatinine levels and renal fibrosis, identifying PTX3 as a promising therapeutic target for CKD.