CXCL13 suppresses liver regeneration through the negative regulation of HGF signaling

• DOI: 10.1038/s41419-025-07568-2
• Publication Date: 2025-05-05T10:01:03Z
• Authors: Qun Zhao; Jingyi Wu; Mengyuan Feng; Anjie Zhang; Liwei Fu; Jinglin Chen; Lian Li; Fangzhou Li; Tingting Li; Shu Jin; Shengbao Li; Xianjun Yu
• Keywords: CXCL13; Liver Regeneration; CXCR5

Abstract Insufficient liver regeneration increases the risk of postoperative failure following transplantation or partial hepatectomy (PHx). Numerous growth factors and cytokines are related to regeneration; however, underlying mechanisms have not been fully elucidated. In this study, CXCL13 was identified as a key factor delaying after PHx. We observed that expression upregulated in PHx mice patients resection. deficiency accelerated regeneration, whereas these effects were abolished by recombinant murine administration. Moreover, proteomics analyses indicated HGF levels serum significantly greater Cxcl13 −/− than WT mice. Further analysis revealed promoted via elevated reparative macrophages subsequent activated HGF/c-MET axis hepatocytes. Additionally, macrophage CXCR5, receptor for CXCL13, augmented Mechanistically, inhibited CXCR5-mediated AKT/FoxO3a signaling. further determined noncanonical NF-κB signaling activation induced hepatic macrophages. Importantly, treatment with CXCL13-neutralizing antibody effectively improved model. Overall, our findings novel function negatively regulating regeneration. The mechanism involved CXCL13/CXCR5-mediated FoxO3a signaling, which downregulated subsequently attenuated hepatocyte proliferation through inactivating These data suggest therapeutic targeting might decrease failure.