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

Abstract

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.