title: Sirt6 deficiency results in progression of glomerular injury in the kidney.
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.
authors.affiliation: Department of Healthcare, Qianfoshan Hospital Affiliated to Shandong University, Jinan, China.|Department of Ophthalmology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
authors.affiliation: Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Woodson
authors.affiliation: Department of Ophthalmology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tilton
authors.affiliation: Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Miller
authors.affiliation: Department of Ophthalmology, University of Texas Medical Branch, Galveston, TX 77555, USA.|Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D018450:Disease Progression; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D037761:Sirtuins / Q000378:metabolism*
chemical_list: C501860:Sirt6 protein, mouse; D037761:Sirtuins
keywords: Sirt6; aging; glomerular injury; podocyte