Sirtuins in Renal Health and Disease

Morigi, Marina; Perico, Luca; Benigni, Ariela

doi:10.1681/asn.2017111218

Cited by 258 publications

(212 citation statements)

References 130 publications

Supporting

Mentioning

208

Contrasting

Unclassified

Order By: Relevance

Section: Introductionmentioning

confidence: 99%

“…Sirtuins belong to the family of conserved nicotinamide adenine dinucleotide-(NAD + -) dependent deacetylases and are involved in stress response, cell proliferation, and antiapoptosis processes [6]. Sirtuin-3 (Sirt3) is localized mainly in the mitochondrial matrix [6]. It plays a pivotal role in maintaining mitochondrial function, protecting against oxidative stress-induced damage by deacetylating lysine residues of mitochondrial proteins, and maintaining the kidney function [7].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

tert-Butylhydroquinone Treatment Alleviates Contrast-Induced Nephropathy in Rats by Activating the Nrf2/Sirt3/SOD2 Signaling Pathway

Zhou

Wang

Shao

et al. 2019

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Oxidative stress plays a critical role in the pathophysiology of contrast-induced nephropathy (CIN). Since the specific treatment of CIN remains an unmet medical need, it is imperative to find an effective strategy against the clinical management of CIN. The transcription factor Nrf2 is known to regulate antioxidative stress response. The aim of the present study was to assess the effects of tert-butylhydroquinone (t-BHQ), an activator of Nrf2, in the prevention of CIN and elucidate the underlying mechanism of its action in vitro and in vivo. We established a rat model of CIN and treated the animals with t-BHQ (25 mg/kg). The effects of t-BHQ treatment on CIN rats were elucidated by assessing renal function, HE staining, immunohistochemistry, and western blotting. We also studied the activity of oxidative stress-related markers, such as intracellular ROS level, MDA level, SOD2 activity, and GSH/GSSG ratio. We validated our results by siRNA-mediated silencing of Nrf2 in HK-2 cells exposed to the radiocontrast agent. Treatment with t-BHQ significantly ameliorated the renal function and the histopathological lesions in CIN rats. Further, pretreatment with t-BHQ significantly increased the SOD2 activity and GSH/GSSG ratio and decreased the levels of ROS and MDA in animals subjected to ioversol exposure. In addition, t-BHQ treatment increased the expression of Nrf2, Sirt3, and SOD2 and concomitantly decreased the expression of acetylated-SOD2. When Nrf2-silenced HK-2 cells were exposed to radiocontrast agent, they suffered severe cell oxidative stress, exhibited lower expression of Sirt3 and SOD2, and expressed higher levels of acetylated-SOD2; however, t-BHQ treatment did not affect the protein expression of these indicators in si-Nrf2 HK-2 cells. Our findings suggested that Nrf2 plays an important role in the regulation of the Sirt3/SOD2 antioxidative pathway, and t-BHQ may be a potential agent to ameliorate radiocontrast-induced nephropathy via activating the Nrf2/Sirt3/SOD2 signaling pathway in vitro and in vivo.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

tert-Butylhydroquinone Treatment Alleviates Contrast-Induced Nephropathy in Rats by Activating the Nrf2/Sirt3/SOD2 Signaling Pathway

Zhou

Wang

Shao

et al. 2019

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…Recently, studies have shown that SIRT1 possesses the ability to inhibit inflammatory response . In the present study, we detected the expression of SIRT1 in TiPs‐treated animal models and macrophages.…”

Section: Resultsmentioning

confidence: 69%

“…Recently, studies have shown that SIRT1 possesses the ability to inhibit inflammatory response. [27][28][29][30] In the present study, we detected the expression of SIRT1 in TiPs-treated animal models and macrophages. As shown in Figure 5A,B, the protein level of SIRT1 was markedly decreased by TiPs compared to the Sham group.…”

Section: Sirt1 Was Downregulated By Tips In Vivo and In Vitromentioning

confidence: 77%

Hydrogen sulfide protects against particle‐induced inflammatory response and osteolysis via SIRT1 pathway in prosthesis loosening

et al. 2020

View full text Add to dashboard Cite

Wear debris‐induced osteolysis and ensuing aseptic loosening is the main cause of implant failure and revision surgery. Wear debris‐induced inflammatory response plays key roles in peri‐implant osteolysis. Recently, substantial of evidence suggests that hydrogen sulfide (H2S), the third gasotransmitter, is a critical player regulating inflammation. However, the role and therapeutic potential of H2S in wear debris‐induced inflammation and osteolysis remains to be defined. In the present study, we investigated the effect of H2S on wear debris‐induced pro‐inflammatory cytokines expression and osteolysis in vitro and in vivo. With a slow‐releasing H2S donor GYY4137, our study demonstrated that H2S attenuated wear debris‐induced osteolysis and osteoclastogenesis in murine calvaria resorption models. The expression of tumor necrosis factor‐alpha (TNF‐α), interleukin‐1β (IL‐1β), and interleukin‐6 (IL‐6) that stimulated by wear particles were significantly reduced by GYY4137. Further, the level of sirtuin 1 (SIRT1), which possesses anti‐inflammation property, was examined in vivo and in macrophages. And we found that wear debris decreased the expression of SIRT1. Cotreated macrophages with GYY4137 in part reversed the decline of SIRT1. More importantly, with the SIRT1 recombinant lentivirus and small interfering RNAs (siRNA) against SIRT1, our data indicated that SIRT1 mediated the inhibitory effects of GYY4137 on wear debris‐induced inflammation. Collectively, these results suggested that exogenous H2S production (via H2S donors) may represent a potential approach for the treatment of wear particle‐induced osteolysis.

show abstract

“…Concurrently, and in accordance with previous studies showing that knockout or inhibition of RAGE prevented CML‐ or LPS‐induced reduction in SIRT1 expression (Grossin et al, ; Huang et al, ), SIRT1 expression was here downregulated in old WT compared with old RAGE −/− mice. Interestingly, reduced renal inflammation and fibrosis have been reported in genetic or pharmacological boosting of SIRT1 models (Hong et al, ; Morigi, Perico, & Benigni, ); on the other hand, its deletion was associated with an aggravation of kidney injuries such as GS (Chuang et al, ). Together, these results suggest a potentially major role for SIRT1 in renal aging.…”

Section: Discussionmentioning

confidence: 99%

Knockout of receptor for advanced glycation end‐products attenuates age‐related renal lesions

et al. 2019

View full text Add to dashboard Cite

Pro‐aging effects of endogenous advanced glycation end‐products (AGEs) have been reported, and there is increasing interest in the pro‐inflammatory and ‐fibrotic effects of their binding to RAGE (the main AGE receptor). The role of dietary AGEs in aging remains ill‐defined, but the predominantly renal accumulation of dietary carboxymethyllysine (CML) suggests the kidneys may be particularly affected. We studied the impact of RAGE invalidation and a CML‐enriched diet on renal aging. Two‐month‐old male, wild‐type (WT) and RAGE−/− C57Bl/6 mice were fed a control or a CML‐enriched diet (200 μg CML/gfood) for 18 months. Compared to controls, we observed higher CML levels in the kidneys of both CML WT and CML RAGE−/− mice, with a predominantly tubular localization. The CML‐rich diet had no significant impact on the studied renal parameters, whereby only a trend to worsening glomerular sclerosis was detected. Irrespective of diet, RAGE−/− mice were significantly protected against nephrosclerosis lesions (hyalinosis, tubular atrophy, fibrosis and glomerular sclerosis) and renal senile apolipoprotein A‐II (ApoA‐II) amyloidosis (p < 0.001). A positive linear correlation between sclerosis score and ApoA‐II amyloidosis score (r = 0.92) was observed. Compared with old WT mice, old RAGE−/− mice exhibited lower expression of inflammation markers and activation of AKT, and greater expression of Sod2 and SIRT1. Overall, nephrosclerosis lesions and senile amyloidosis were significantly reduced in RAGE−/− mice, indicating a protective effect of RAGE deletion with respect to renal aging. This could be due to reduced inflammation and oxidative stress in RAGE−/− mice, suggesting RAGE is an important receptor in so‐called inflamm‐aging.

show abstract

Sirtuins in Renal Health and Disease

Cited by 258 publications

References 130 publications

tert-Butylhydroquinone Treatment Alleviates Contrast-Induced Nephropathy in Rats by Activating the Nrf2/Sirt3/SOD2 Signaling Pathway

tert-Butylhydroquinone Treatment Alleviates Contrast-Induced Nephropathy in Rats by Activating the Nrf2/Sirt3/SOD2 Signaling Pathway

Hydrogen sulfide protects against particle‐induced inflammatory response and osteolysis via SIRT1 pathway in prosthesis loosening

Knockout of receptor for advanced glycation end‐products attenuates age‐related renal lesions

Contact Info

Product

Resources

About