The role of Sirt3-induced autophagy in renal structural damage caused by periodontitis in rats

J Periodontal Res. 2023 Feb;58(1):97-108. doi: 10.1111/jre.13071. Epub 2022 Nov 15.

Abstract

Objective: This research aimed to explore the effect of periodontitis on renal tissues injury in rats and the role of Sirtuin3 (Sirt3) and its regulation of autophagy in this progression.

Material and methods: Thirty Wistar rats were assigned into three groups: control, periodontitis (P), and periodontitis with gavage administration of Sirt3 activator resveratrol (P + RSV). To induce periodontitis, the wire ligature was placed around the cervical region of the rat maxillary first molar. After 8 weeks, micro-computed tomography (Micro-CT) and hematoxylin and eosin (HE) were used to evaluate the alveolar bone resorption and periodontal inflammation. Serum and urine biochemical indicators were measured to assess renal function. The pathological changes of the kidney were observed via HE and periodic acid Schiff (PAS) staining. Autophagosome was viewed by transmission electron microscopy (TEM). Real-time PCR and western blot were used to test expressions of Sirt3 and autophagy indicators in renal and periodontal tissues, including mammalian target of rapamycin (mTOR), phosphor-mTOR (p-mTOR), BECN1 (Beclin-1), and microtubule-associated protein 1 light chain 3 (LC3).

Results: Alveolar bone destruction, resorption, and periodontal inflammation were observed in the P group (compared with the control group), and the above indexes were significantly improved after RSV intervention; the obvious changes in renal tissue structure in the P group were partially recovered after RSV intervention, while renal functional status was not affected (among the three groups); in addition, the levels of Sirt3 and autophagy in kidney and periodontal tissues of P group were inhibited, manifested as a decrease in the number of autophagosomes (renal tissue) and expressions of autophagy marker Beclin-1 and LC3 conversion rate and an increase in the expression of p-mTOR. After Sirt3 activation (RSV), the above indicators were significantly improved.

Conclusion: Periodontitis causes renal structural damage in rats, which may be connected to the effect of Sirt3-induced autophagy.

Keywords: Sirt3; autophagy; kidney; periodontitis.

MeSH terms

  • Alveolar Bone Loss* / pathology
  • Animals
  • Autophagy
  • Beclin-1 / metabolism
  • Beclin-1 / pharmacology
  • Inflammation
  • Kidney / metabolism
  • Kidney / pathology
  • Periodontitis* / pathology
  • Rats
  • Rats, Wistar
  • Sirtuin 3*
  • TOR Serine-Threonine Kinases / metabolism
  • TOR Serine-Threonine Kinases / pharmacology
  • X-Ray Microtomography

Substances

  • Beclin-1
  • Sirtuin 3
  • TOR Serine-Threonine Kinases
  • SIRT3 protein, rat