Aging
Navigate
Submit an Article
Research Paper|Volume 9, Issue 3|pp 1069—1083

Sirt6 deficiency results in progression of glomerular injury in the kidney

Wen Huang1,2, Hua Liu3, Shuang Zhu2, Michael Woodson4, Rong Liu2, Ronald G. Tilton5, Jordan D. Miller7, Wenbo Zhang2,6
  • 1Department of Healthcare, Qianfoshan Hospital Affiliated to Shandong University, Jinan, China
  • 2Department of Ophthalmology, University of Texas Medical Branch, Galveston, TX 77555, USA
  • 3Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, TX 77555, USA
  • 4Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA
  • 5Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA
  • 6Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA
  • 7Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA

* * Equal contribution

Received: February 27, 2016Accepted: March 18, 2017Published: March 28, 2017
https://doi.org/10.18632/aging.101214

Copyright: © 2017 Huang 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

Aging is associated with an increased incidence and prevalence of renal glomerular diseases. Sirtuin (Sirt) 6, a nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase, has been shown to protect against multiple age-associated phenotypes; however it is unknown whether Sirt6 has a direct pathophysiologic role in the kidney. In the present study, we demonstrate that Sirt6 is expressed in the kidney and aging Sirt6-deficient mice exhibit renal hypertrophy with glomerular enlargement. Sirt6 deletion induces podocyte injury, including decreases in slit diaphragm proteins, foot process effacement, and cellular loss, resulting in proteinuria. Knockdown of Sirt6 in cultured primary murine podocytes induces shape changes with loss of process formation and cell apoptosis. Moreover, Sirt6 deficiency results in progressive renal inflammation and fibrosis. Collectively, these data provide compelling evidence that Sirt6 is important for podocyte homeostasis and maintenance of glomerular function, and warrant further investigation into the role of Sirt6 in age-associated kidney dysfunction.