Research Paper Volume 9, Issue 3 pp 1069—1083
Sirt6 deficiency results in progression of glomerular injury in the kidney
- 1 Department of Healthcare, Qianfoshan Hospital Affiliated to Shandong University, Jinan, China
- 2 Department of Ophthalmology, University of Texas Medical Branch, Galveston, TX 77555, USA
- 3 Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, TX 77555, USA
- 4 Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA
- 5 Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA
- 6 Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA
- 7 Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA
Received: February 27, 2016 Accepted: March 18, 2017 Published: March 28, 2017
https://doi.org/10.18632/aging.101214How to Cite
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.