Research Paper Volume 11, Issue 4 pp 1151—1162

DR region specific antibody ameliorated but ouabain worsened renal injury in nephrectomized rats through regulating Na,K-ATPase mediated signaling pathways

Juan Wang 1, 2, 3, , Sayyed Hanif Ullah 1, , Meihe Li 4, , Miao Zhang 4, , Fujun Zhang 1, , Jin Zheng 4, , Xiaofei Yan 1, ,

  • 1 Department of Biochemistry and Molecular Biology, Medical College of Xi'an Jiaotong University, Xi'an 710061, China
  • 2 Department of Pathology, Medical College of Xi'an Jiaotong University, Xi'an 710061, China
  • 3 Department of Pathology, Ankang Central Hostipal, An’kang 725000, China
  • 4 Hospital of Nephrology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China

received: December 10, 2018 ; accepted: February 1, 2019 ; published: February 26, 2019 ;

https://doi.org/10.18632/aging.101815
How to Cite

Copyright: Wang 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.

Abstract

Reduced Na+-K+-ATPase function is reported in various renal diseases. This implies that increase of Na+-K+-ATPase function may be a new target in treatment of renal injury. We previously reported that Na+-K+-ATPase was stabilized by DRm217, a specific antibody against DR region of Na+-K+-ATPase. In this study, we compared the protective effect of DRm217 and ouabain on kidney in a chronic kidney disease rat model and investigated the mechanism under it. We found that DRm217 improved renal function, alleviated glomerulus atrophy, inhibited renal tubular cells apoptosis, tubulointerstitial injury and renal fibrosis in 5/6 nephrectomized rats. Contrary to DRm217, ouabain worsened renal damage. Activated Na+-K+-ATPase /Src signaling pathway, increased oxidant stress and activated inflammasome were responsible for nephrectomized or ouabain-induced renal injury. DRm217 inhibited Na+-K+-ATPase /Src signaling pathway, retarded oxidant stress, suppressed inflammasome activation, and improved renal function, suggesting a novel approach to prevent renal damage.

Abbreviations

Src: Proto-oncogene tyrosine-protein kinase Src; CKD: Chronic kidney disease; BUN: Blood urea nitrogen; TUNEL: transferase-mediated deoxyuridine triphosphate-biotin nick end labeling; NLRP3: NACHT, LRR and PYD domains-containing protein 3; IL-1β: interleukin 1β; IL-18: interleukin 18; GSI: Glomerulosclerotic Index; TIS: Tubule interstitial score; ELISA: enzyme-linked immunosorbent assay; AngII: Angiotensin II.