Abstract

Zinc transporter 8 (ZnT8) transports zinc ions for crystallization and storage of insulin in pancreatic beta-cells and ZnT8 dysfunction is involved in pathogenesis of diabetes. The current study aimed to investigate whether ZnT8 has effects in pathophysiology of diabetic kidney disease (DKD) by using animal models for diabetes, including STZ-induced diabetic, db/db, ZnT8-KO, ZnT8-KO-STZ and ZnT8-KO-db/db mice. Results demonstrated that urine albumin to creatinine ratio and epithelial-to-mesenchymal transition (EMT) were increased in kidneys of ZnT8-KO-STZ and ZnT8-KO-db/db mice compared with C57BL/6 J and ZnT8-KO mice, while serum TGF-β1, IL-6, and TNF-α levels were elevated in parallel. In kidneys of mice intercrossed between ZnT8-KO and STZ-induced diabetic or db/db mice, these three inflammatory factors, ACR and EMT were also found to be increased compared with C57BL/6J, db/db and ZnT8-KO mice. Furthermore, ZnT8 up-regulation by hZnT8-EGFP reduced the levels of high glucose (HG)-induced EMT and inflammatory factors in normal rat kidney tubular epithelial cell (NRK-52E cells). Expression of phosphorylated Smad2/Smad3 was up-regulated after HG stimulation and further enhanced by ZnT8 siRNA but down-regulated after hZnT8-EGFP gene transfection. The current study thus provides the first evidence that ZnT8 protects against EMT-tubulointerstitial fibrosis though the restrain of TGF-β1/Smads signaling activation in DKD.

Details

Title
Effects of ZnT8 on epithelial-to-mesenchymal transition and tubulointerstitial fibrosis in diabetic kidney disease
Author
Zhang, Xiuli 1 ; Guan Tingwen 2 ; Yang Boxuan 2 ; Gu, Harvest F 3   VIAFID ORCID Logo  ; Chi Zhihong 2 

 The First Affiliated Hospital of Shenzhen University, Department of Nephrology, Second People’s Hospital, Shenzhen, P.R. China (GRID:grid.263488.3) (ISNI:0000 0001 0472 9649); China Medical University, Department of Pathophysiology, Shenyang, P.R. China (GRID:grid.412449.e) (ISNI:0000 0000 9678 1884) 
 China Medical University, Department of Pathophysiology, Shenyang, P.R. China (GRID:grid.412449.e) (ISNI:0000 0000 9678 1884) 
 China Pharmaceutical University, Center for Pathophysiology, School of Basic Medicine and Clinical Pharmacy, Nanjing, P.R. China (GRID:grid.254147.1) (ISNI:0000 0000 9776 7793) 
Publication year
2020
Publication date
Jul 2020
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2424566189
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.