Research Paper Volume 13, Issue 5 pp 6782—6803

The role of CDX2 in renal tubular lesions during diabetic kidney disease

Huiming Liu1,2,4, , Rui Yan3, , Luqun Liang1,2, , Huifang Zhang1,2, , Jiayi Xiang1,2, , Lingling Liu1,2, , Xiaohuan Zhang1,2, , Yanwen Mao1,2, , Wei Peng1,2, , Ying Xiao1,2, , Fan Zhang1,2, , Yuxia Zhou1,2, , Mingjun Shi1,2, , Yuanyuan Wang1,2, , Bing Guo1,2, ,

  • 1 Department of Pathophysiology, Guizhou Medical University, Guiyang 550025, Guizhou, China
  • 2 Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang 550025, Guizhou, China
  • 3 Department of Nephrology, Affiliated Hospital of Guizhou Medical University, Guiyang 550025, Guizhou, China
  • 4 Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China

Received: June 15, 2020       Accepted: December 9, 2020       Published: February 17, 2021
How to Cite

Copyright: © 2021 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Renal tubules are vulnerable targets of various factors causing kidney injury in diabetic kidney disease (DKD), and the degree of tubular lesions is closely related to renal function. Abnormal renal tubular epithelial cells (RTECs) differentiation and depletion of cell junction proteins are important in DKD pathogenesis. Caudal-type homeobox transcription factor 2 (CDX2), represents a key nuclear transcription factor that maintains normal proliferation and differentiation of the intestinal epithelium. The present study aimed to evaluate the effects of CDX2 on RTECs differentiation and cell junction proteins in DKD. The results demonstrated that CDX2 was mainly localized in renal tubules, and downregulated in various DKD models. CDX2 upregulated E-cadherin and suppressed partial epithelial-mesenchymal transition (EMT), which can alleviate hyperglycemia-associated RTECs injury. Cystic fibrosis transmembrane conductance regulator (CFTR) was regulated by CDX2 in NRK-52E cells, and CFTR interfered with β-catenin activation by binding to Dvl2, which is an essential component of Wnt/β-catenin signaling. CFTR knockdown abolished the suppressive effects of CDX2 on Wnt/β-catenin signaling, thereby upregulating cell junction proteins and inhibiting partial EMT in RTECs. In summary, CDX2 can improve renal tubular lesions during DKD by increasing CFTR amounts to suppress the Wnt/β-catenin signaling pathway.


DKD: Diabetic kidney disease; RTECs: Renal tubular epithelial cells; CDX2: Caudal-type homeobox transcription factor 2; EMT: Epithelial-mesenchymal transition; CFTR: Cystic fibrosis transmembrane conductance regulator; ESRD: End-Stage Renal Disease; UUO: Unilateral ureteral obstruction; STZ: Streptozocin; T1D: Type 1 diabetes; T2D: Type 2 diabetes; PAS: Periodic acid-Schiff; DMEM: Dulbecco's modified Eagle's medium; FBS: Fetal bovine serum; NG: Normal glucose; HG: High glucose; α-SMA: α-smooth muscle actin; Col III: Collagen III.