PPDPF preserves integrity of proximal tubule by modulating NMNAT activity in chronic kidney diseases

Authors: Xiaoliang Fang, Yi Zhong, Rui Zheng, Qihui Wu, Yu Liu, Dexin Zhang, Yuwei Wang, Wubing Ding, Kaiyuan Wang, Fengbo Zhong, Kai Lin, Xiaohui Yao, Qingxun Hu, Xiaofei Li, Guofeng Xu, Na Liu, Jing Nie, Dali Li, Hongquan Geng, Yuting Guan

Published: 2025-03-19

DOI: 10.1126/sciadv.adr8648

Source: Full article


Abstract

Genome-wide association studies (GWAS) have identified loci associated with kidney diseases, but the causal variants, genes, and pathways involved remain elusive. Here, we identified a kidney disease gene called pancreatic progenitor cell differentiation and proliferation factor (PPDPF) through integrating GWAS on kidney function and multiomic analysis. PPDPF was predominantly expressed in healthy proximal tubules of human and mouse kidneys via single-cell analysis. Further investigations revealed that PPDPF functioned as a thiol-disulfide oxidoreductase to maintain cellular NAD