Role and Mechanism of NUP160-regulated Autophagy in Pathogenesis of Diabetic Nephropathy

Authors

  • Jiayong Xie Department of Nephrology,Xinghua People’s Hospital, China Author
  • Ying Yuan Department of Nephrology,Xinghua People’s Hospital, China Author
  • Gang Yao Department of Nephrology, Second Affiliated Hospital of Nanjing Medical University, China Author
  • Wenjuan Yu Department of Nephrology, Second Affiliated Hospital of Nanjing Medical University, China Author
  • Qiang Zhu Department of Nephrology,Xinghua People’s Hospital, China Author

Abstract

\Introduction. Diabetes mellitus (DM) is one of the most common chronic diseases worldwide, and diabetic nephropathy (DN) is the most significant complication of DM, which is highly prevalent and difficult to cure. This research project aims to investigate the role and mechanism of Nucleoporin 160kDa (NUP160)-regulated autophagy in the pathogenesis of DN. Methods. NUP160 levels in diabetic and non-diabetic kidney tissues were measured by Western blot, and the connection between NUP160 and renal function of DN patients was analyzed. The podocytes were divided into four groups, namely the standard group (culture medium: standard glucose solution), high glucose (HG) group (HG solution), HG+si-NUP160 group (HG solution+si-NUP160 transfection) and HG+si-NC group (HG solution+si-NUP 160 transfection) for the determination of apoptosis by flow cytometry and measurements of LC3B, Prostacyclin-62 (P62), Janus kinase 2 (JAK2) and Signal transducer and activator of transcription3 (STAT3) by Western blot. Results. In DN patients, NUP160 decreased in podocytes and was inversely proportional to Blood urea nitrogen (BUN), Serum creatinine (Scr) and β2-Microglobulin (β2-MG) (P < .05). Compared with a standard group, the apoptosis rate, P62 level, and the ratios of phosphorylation-JAK2 (p-JAK2)/JAK2, phosphorylation-STAT3 (p-STAT3)/STAT3, and LC3B-Ⅱ/LC3B-Ⅰ elevated in the other three groups (P < .05). Apoptosis rate and P62 level, p-JAK2/JAK2 and p-STAT3/STAT3 ratios increased, and LC3B-Ⅱ/LC3B-Ⅰ ratio decreased in the HG+si-NUP160 group (P < .05), while those in HG+si-NC group showed no evident changes, compared with HG group (P > .05). Conclusion. NUP160 is downregulated in DN and can affect cellular autophagy through the activation of JAK2/STAT3 signaling pathway.

 

DOI: 10.52547/ijkd.7884

Downloads

Download data is not yet available.

Downloads

Published

2023-12-03

Issue

Section

ORIGINAL | Kidney Diseases

How to Cite

Role and Mechanism of NUP160-regulated Autophagy in Pathogenesis of Diabetic Nephropathy. (2023). Iranian Journal of Kidney Diseases, 17(6), 327-334. https://ijkd.org/index.php/ijkd/article/view/7884