Sirtuins: Research advances on the therapeutic role in acute kidney injury

Huang, Chaoming; Jiang, Shisheng; Gao, Shuhan; Wang, Yuxin; Cai, Xiao-Ting; Fang, Junyan; Yan, Tingdong; Wan, Chunpeng; Cai, Yi

doi:10.1016/j.phymed.2022.154122

Cited by 20 publications

(16 citation statements)

References 82 publications

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“… 42 – 44 The renoprotective effects of SirT3-ROS pathway also have been reported in AKI. 28 , 35 , 45 , 46 In the current research, we observed that cisplatin decreased the expression of SirT3 in the injured kidneys and TECs, and FFAR4 activation recovered cisplatin-induced reduction of SirT3. Hence, we hypothesized that FFAR4 may facilitate SirT3 expression, thereby improving cellular senescence in AKI induced by cisplatin.…”

Section: Discussionsupporting

confidence: 54%

FFAR4 improves the senescence of tubular epithelial cells by AMPK/SirT3 signaling in acute kidney injury

Yang

Wang

Guo

et al. 2022

Sig Transduct Target Ther

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Acute kidney injury (AKI) is a serious clinical complication with high morbidity and mortality rates. Despite substantial progress in understanding the mechanism of AKI, no effective therapy is available for treatment or prevention. We previously found that G protein-coupled receptor (GPCR) family member free fatty acid receptor 4 (FFAR4) agonist TUG891 alleviated kidney dysfunction and tubular injury in AKI mice. However, the versatile role of FFAR4 in kidney has not been well characterized. In the study, the expression of FFAR4 was abnormally decreased in tubular epithelial cells (TECs) of cisplatin, cecal ligation/perforation and ischemia/reperfusion injury-induced AKI mice, respectively. Systemic and conditional TEC-specific knockout of FFAR4 aggravated renal function and pathological damage, whereas FFAR4 activation by TUG-891 alleviated the severity of disease in cisplatin-induced AKI mice. Notably, FFAR4, as a key determinant, was firstly explored to regulate cellular senescence both in injured kidneys of AKI mice and TECs, which was indicated by senescence-associated β-galactosidase (SA-β-gal) activity, marker protein p53, p21, Lamin B1, phospho-histone H2A.X, phospho-Rb expression, and secretory phenotype IL-6 level. Mechanistically, pharmacological activation and overexpression of FFAR4 reversed the decrease of aging-related SirT3 protein, where FFAR4 regulated SirT3 expression to exhibit anti-senescent effect via Gq subunit-mediated CaMKKβ/AMPK signaling in cisplatin-induced mice and TECs. These findings highlight the original role of tubular FFAR4 in cellular senescence via AMPK/SirT3 signaling and identify FFAR4 as a potential drug target against AKI.

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Section: Discussionsupporting

confidence: 54%

FFAR4 improves the senescence of tubular epithelial cells by AMPK/SirT3 signaling in acute kidney injury

Yang

Wang

Guo

et al. 2022

Sig Transduct Target Ther

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“…SIRT1 has dual cellular localization and can be found in both the nucleus and the cytoplasm [ 92 ]. SIRT1 is mainly present in the nucleus, but there are also small amounts of SIRT1 distributed in the cytoplasm [ 93 ]. In addition, research on Resveratrol, an activator of SIRT1, and its impact on diabetic nephropathy, demonstrates Sirt1 expression in adult kidneys of humans, mice, and rats, with SIRT1 distribution seen in the nucleus of the glomeruli.…”

Section: Discussionmentioning

confidence: 99%

Tenovin-1 Ameliorates Renal Fibrosis in High-Fat-Diet-Induced Diabetic Nephropathy via Antioxidant and Anti-Inflammatory Pathways

et al. 2022

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High-fat diet (HFD)-induced obesity has been involved in the development of diabetic nephropathy (DN). Tenovin-1, a potent selective SIRT1/2 inhibitor, regulates various target proteins. The present study evaluated the protective effect of Tenovin-1 against renal fibrosis in HFD-induced Zucker diabetic fatty (ZDF) rats. Rats were fed a normal chow diet or HFD. Tenovin-1 (45 mg/kg) administered to HFD-fed rats decreased inflammatory cytokine expression in the serum of the rats. The antioxidant status and oxidative damage to lipids or DNA were significantly restored by Tenovin-1. Additionally, Tenovin-1 reduced the levels of blood urea nitrogen (BUN), serum creatinine (sCr), microalbumin, and urinary protein-based biomarkers in the urine of HFD-fed rats. The abnormal architecture of the kidney and pancreas was restored by Tenovin-1 administration. Tenovin-1 also reduced apoptosis in the kidneys of the HFD-fed rats and HG-treated NRK-52E cells. It significantly lowered the levels of ECM proteins in the kidneys of HFD-fed rats and HG-treated NRK-52E cells. Additionally, Tenovin-1 markedly reduced claudin-1, SIRT1, and SIRT2, but increased SIRT3 and SIRT4 in HFD-fed rats and NRK-52E cells treated with HG. Furthermore, Tenovin-1 altered epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor-β (PDGFR-β), and signal transducer and activator of transcription 3 (STAT3) levels in the kidneys of HFD-fed rats. Conclusively, this study shows that Tenovin-1 can be a potential candidate drug for the treatment of HFD-induced renal fibrosis, in vivo and in vitro models.

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“…On one hand, it exhibits renoprotective effects and improves mitochondrial function through scavenging mitochondrial ROS directly ( Trujillo et al, 2013 ). On the other hand, it can alleviate mitochondrial oxidative stress via the activation of Nrf2, Sirtuin-1 and Sirtuin-3 ( Molina-Jijón et al, 2011 ; Tapia et al, 2012 ; Martínez-Morúa et al, 2013 ; Trujillo et al, 2013 ; Huang et al, 2022a ; Liu et al, 2022c ). Curcumin can activate Nrf2 signaling pathway via inhibiting Keap1, upregulating Nrf2 and inducing the nuclear translocation of Nrf2 ( Ashrafizadeh et al, 2020 ).…”

Section: Natural Products For Regulating Mitochondrial Functionmentioning

confidence: 99%

Natural products for kidney disease treatment: Focus on targeting mitochondrial dysfunction

2023

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The patients with kidney diseases are increasing rapidly all over the world. With the rich abundance of mitochondria, kidney is an organ with a high consumption of energy. Hence, renal failure is highly correlated with the breakup of mitochondrial homeostasis. However, the potential drugs targeting mitochondrial dysfunction are still in mystery. The natural products have the superiorities to explore the potential drugs regulating energy metabolism. However, their roles in targeting mitochondrial dysfunction in kidney diseases have not been extensively reviewed. Herein, we reviewed a series of natural products targeting mitochondrial oxidative stress, mitochondrial biogenesis, mitophagy, and mitochondrial dynamics. We found lots of them with great medicinal values in kidney disease. Our review provides a wide prospect for seeking the effective drugs targeting kidney diseases.

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Sirtuins: Research advances on the therapeutic role in acute kidney injury

Cited by 20 publications

References 82 publications

FFAR4 improves the senescence of tubular epithelial cells by AMPK/SirT3 signaling in acute kidney injury

FFAR4 improves the senescence of tubular epithelial cells by AMPK/SirT3 signaling in acute kidney injury

Tenovin-1 Ameliorates Renal Fibrosis in High-Fat-Diet-Induced Diabetic Nephropathy via Antioxidant and Anti-Inflammatory Pathways

Natural products for kidney disease treatment: Focus on targeting mitochondrial dysfunction

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