Sirt6 deficiency results in progression of glomerular injury in the kidney

Wen Huang, Hua Liu, Shuang Zhu, Michael Woodson, Rong Liu, Ronald Tilton, Jordan D. Miller, Wenbo Zhang

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1069-1083
Number of pages15
JournalAging
Volume9
Issue number3
DOIs
StatePublished - 2017

Fingerprint

Kidney
Podocytes
Wounds and Injuries
Histone Deacetylases
Diaphragm
Proteinuria
NAD
Hypertrophy
Foot
Homeostasis
Fibrosis
Maintenance
Apoptosis
Inflammation
Phenotype
Incidence
Proteins

Keywords

  • Aging
  • Glomerular injury
  • Podocyte
  • Sirt6

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Sirt6 deficiency results in progression of glomerular injury in the kidney. / Huang, Wen; Liu, Hua; Zhu, Shuang; Woodson, Michael; Liu, Rong; Tilton, Ronald; Miller, Jordan D.; Zhang, Wenbo.

In: Aging, Vol. 9, No. 3, 2017, p. 1069-1083.

Research output: Contribution to journalArticle

Huang, W, Liu, H, Zhu, S, Woodson, M, Liu, R, Tilton, R, Miller, JD & Zhang, W 2017, 'Sirt6 deficiency results in progression of glomerular injury in the kidney', Aging, vol. 9, no. 3, pp. 1069-1083. https://doi.org/10.18632/aging.101214
Huang, Wen ; Liu, Hua ; Zhu, Shuang ; Woodson, Michael ; Liu, Rong ; Tilton, Ronald ; Miller, Jordan D. ; Zhang, Wenbo. / Sirt6 deficiency results in progression of glomerular injury in the kidney. In: Aging. 2017 ; Vol. 9, No. 3. pp. 1069-1083.
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