Regulon analysis identifies protective FXR and CREB5 in proximal tubules in early diabetic kidney disease

BMC Nephrology

Research

Wanting Shi¹  Weibo Le¹  Jingsong Shi¹  Shaolin Shi¹  Qiaoli Tang² 

[1] National Clinical Research Center for Kidney Disease, Affiliated Jinling Hospital, Medical School, Nanjing University, Nanjing, China;National Clinical Research Center for Kidney Disease, Affiliated Jinling Hospital, Medical School, Nanjing University, Nanjing, China;Department of Nephrology, the First Affiliated Hospital of University of Science and Technology of China, Hefei, China;

关键词: Diabetic kidney disease;    Single nucleus RNA-seq;    Gene regulatory network;    Proximal tubule epithelial cells;    FXR;    CREB5;   

DOI  :  10.1186/s12882-023-03239-6

 received in 2022-12-17, accepted in 2023-06-09,  发布年份 2023

来源: Springer

【 摘 要 】

Diabetic kidney disease (DKD) is the most common complication of diabetes mellitus and a leading cause of kidney failure worldwide. Despite its prevalence, the mechanisms underlying early kidney damage in DKD remain poorly understood. In this study, we used single nucleus RNA-seq to construct gene regulatory networks (GRNs) in the kidney cortex of patients with early DKD. By comparing these networks with those of healthy controls, we identify cell type-specific changes in genetic regulation associated with diabetic status. The regulon activities of FXR (NR1H4) and CREB5 were found to be upregulated in kidney proximal convoluted tubule epithelial cells (PCTs), which were validated using immunofluorescence staining in kidney biopsies from DKD patients. In vitro experiments using cultured HK2 cells showed that FXR and CREB5 protected cells from apoptosis and epithelial–mesenchymal transition. Our findings suggest that FXR and CREB5 may be promising targets for early intervention in patients with DKD.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 1

41116_2023_37_Article_IEq123.gif

41116_2023_37_Article_IEq118.gif

41116_2023_37_Article_IEq116.gif

Fig. 3

41116_2023_37_Article_IEq99.gif

41116_2023_37_Article_IEq73.gif

41116_2023_37_Article_IEq65.gif