Absence of Sirt3 aggravates cisplatin nephrotoxicity via enhanced renal tubular apoptosis and inflammation

Kim, Dal; Park, Woong; Lee, Sik; Kim, Won; Park, Sung Kwang; Kang, Kyung Pyo

doi:10.3892/mmr.2018.9350

Cited by 16 publications

(17 citation statements)

References 40 publications

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“…Another study reported that SIRT3 could diminish inflammation and mitigated endotoxin‐induced acute lung injury (ALI), suggesting that the induction/activation of SIRT3 may serve as a new therapeutic strategy in ALI. Besides, SIRT3 deficiency aggravated cisplatin‐induced nephrotoxicity mainly by increasing renal inflammation . The current study showed that SIRT3 expression was increased by celastrol treatment in liver fibrosis, showing that SIRT3 is essential for the liver protection effect of celastrol against liver fibrosis.…”

Section: Discussionmentioning

confidence: 51%

Celastrol exerts anti‐inflammatory effect in liver fibrosis via activation of AMPK‐SIRT3 signalling

Wang

et al. 2019

J Cellular Molecular Medi

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Celastrol, a pentacyclic tritepene extracted from Tripterygium Wilfordi plant, showing potent liver protection effects on several liver‐related diseases. However, the anti‐inflammatory potential of celastrol in liver fibrosis and the detailed mechanisms remain uncovered. This study was to investigate the anti‐inflammatory effect of celastrol in liver fibrosis and to further reveal mechanisms of celastrol‐induced anti‐inflammatory effects with a focus on AMPK‐SIRT3 signalling. Celastrol showed potent ameliorative effects on liver fibrosis both in activated hepatic stellate cells (HSCs) and in fibrotic liver. Celastrol remarkably suppressed inflammation in vivo and inhibited the secretion of inflammatory factors in vitro. Interestingly, celastrol increased SIRT3 promoter activity and SIRT3 expression both in fibrotic liver and in activated HSCs. Furthermore, SIRT3 silencing evidently ameliorated the anti‐inflammatory potential of celastrol. Besides, we found that celastrol could increase the AMPK phosphorylation. Further investigation showed that SIRT3 siRNA decreased SIRT3 expression but had no obvious effect on phosphorylation of AMPK. In addition, inhibition of AMPK by employing compound C (an AMPK inhibitor) or AMPK1α siRNA significantly suppressed SIRT3 expression, suggesting that AMPK was an up‐stream protein of SIRT3 in liver fibrosis. We further found that depletion of AMPK significantly attenuated the inhibitory effect of celastrol on inflammation. Collectively, celastrol attenuated liver fibrosis mainly through inhibition of inflammation by activating AMPK‐SIRT3 signalling, which makes celastrol be a potential candidate compound in treating or protecting against liver fibrosis.

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Section: Discussionmentioning

confidence: 51%

Celastrol exerts anti‐inflammatory effect in liver fibrosis via activation of AMPK‐SIRT3 signalling

Wang

et al. 2019

J Cellular Molecular Medi

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“…SIRT3 has been reported to have a protective effect against cardiac hypertrophy and interstitial fibrosis by augmenting antioxidant defense mechanisms [15]. We also reported that the absence of SIRT3 enhances cisplatin-induced renal inflammation and tubular apoptosis [16]. In aged mice, the SIRT3/TGF-β1 interaction plays an important role in the pathophysiology of pulmonary fibrosis [17].…”

Section: Introductionmentioning

confidence: 84%

“…The block was cut into 5 µm sections and stained with periodic acid-Schiff stain (PAS) and Masson's trichrome. Immunohistochemical staining was performed as described previously [16,25,38]. Tissue sections were deparaffinized with xylene, rehydrated through graded washes of ethanol in water, and rinsed in pure water.…”

Section: Histologic Examinationmentioning

confidence: 99%

Sirtuin 3 Activation by Honokiol Decreases Unilateral Ureteral Obstruction-Induced Renal Inflammation and Fibrosis via Regulation of Mitochondrial Dynamics and the Renal NF-κB-TGF-β1/Smad Signaling Pathway

Quan

Park

Jin

et al. 2020

IJMS

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Renal fibrosis is a common feature of all progressive chronic kidney diseases. Sirtuin 3 (SIRT3) is one of the mitochondrial sirtuins, and plays a role in the regulation of mitochondrial biogenesis, oxidative stress, fatty acid metabolism, and aging. Recently, honokiol (HKL), as a pharmaceutical SIRT3 activator, has been observed to have a protective effect against pressure overload-induced cardiac hypertrophy by increasing SIRT3 activity. In this study, we investigated whether HKL, as a SIRT3 activator, also has protective effects against unilateral ureteral obstruction (UUO)-induced renal tubulointerstitial fibrosis through SIRT3-dependent regulation of mitochondrial dynamics and the nuclear factor-κB (NF-κB)/transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. We found that HKL decreased the UUO-induced increase in tubular injury and extracellular matrix (ECM) deposition in mice. HKL also decreased myofibroblast activation and proliferation in UUO kidneys and NRK-49F cells. Finally, we showed that HKL treatment decreased UUO-induced mitochondrial fission and promoted mitochondrial fusion through SIRT3-dependent effects. In conclusion, activation of SIRT3 via HKL treatment might have beneficial effects on UUO-induced renal fibrosis through SIRT3-dependent regulation of mitochondrial dynamics and the NF-κB/TGF-β1/Smad signaling pathway.

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“…SIRT3 can also protect against sepsis-induced AKI by promoting autophagy via upregulating p-AMPK and downregulating phosphor-mammalian target of rapamycin (p-mTOR) ( Zhao et al, 2018 ). SIRT3 deficiency can increase renal tubular apoptosis and inflammation and aggravate renal injury ( Kim et al, 2018 ). Recent studies suggest that SIRT3 may regulate fatty acid oxidation (FAO) by deacetylating liver kinase B1 and activating AMP-activated protein kinase to reduce cisplatin-induced AKI in mice ( Li et al, 2020 ).…”

Section: Class III Histone Deacetylases and Acute Kidney Injurymentioning

confidence: 99%

The Role and Mechanism of Histone Deacetylases in Acute Kidney Injury

et al. 2021

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Acute kidney injury (AKI) is a common clinical complication with an incidence of up to 8–18% in hospitalized patients. AKI is also a complication of COVID-19 patients and is associated with an increased risk of death. In recent years, numerous studies have suggested that epigenetic regulation is critically involved in the pathophysiological process and prognosis of AKI. Histone acetylation, one of the epigenetic regulations, is negatively regulated by histone deacetylases (HDACs). Increasing evidence indicates that HDACs play an important role in the pathophysiological development of AKI by regulation of apoptosis, inflammation, oxidative stress, fibrosis, cell survival, autophagy, ATP production, and mitochondrial biogenesis (MB). In this review, we summarize and discuss the role and mechanism of HDACs in the pathogenesis of AKI.

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Absence of Sirt3 aggravates cisplatin nephrotoxicity via enhanced renal tubular apoptosis and inflammation

Cited by 16 publications

References 40 publications

Celastrol exerts anti‐inflammatory effect in liver fibrosis via activation of AMPK‐SIRT3 signalling

Celastrol exerts anti‐inflammatory effect in liver fibrosis via activation of AMPK‐SIRT3 signalling

Sirtuin 3 Activation by Honokiol Decreases Unilateral Ureteral Obstruction-Induced Renal Inflammation and Fibrosis via Regulation of Mitochondrial Dynamics and the Renal NF-κB-TGF-β1/Smad Signaling Pathway

The Role and Mechanism of Histone Deacetylases in Acute Kidney Injury

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