Pharmacological Activation of Sirt1 Ameliorates Cisplatin-Induced Acute Kidney Injury by Suppressing Apoptosis, Oxidative Stress, and Inflammation in Mice

Kim, Jung-Yeon; Jo, Jungmin; Kim, Kiryeong; An, Hyun‐Jin; Gwon, Mi‐Gyeong; Gu, Hyemin; Kim, Hyun-Ju; Yang, Aicheng; Kim, Sung Woo; Jeon, Eon Ju; Park, Jae-Hyung; Leem, Jaechan; Park, Kwan‐Kyu

doi:10.3390/antiox8080322

Cited by 58 publications

(60 citation statements)

References 43 publications

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“…Images were captured using a confocal microscope (Nikon, Tokyo, Japan). Tubular injury in PAS-stained sections was assessed and scored at a ×200 magnification using 10 randomly selected fields for each kidney as follows: 0, 0%; 1, ≤10%; 2, 11-25%; 3, 26-45%; 4, 46-75%; and 5, 76-100% [18]. For IHC staining, the sections were incubated with primary antibodies against kidney injury molecule-1 (Kim-1; Abcam, Cambridge, MA, USA), neutrophil gelatinase-associated lipocalin (NGAL; Santa Cruz Biotechnology, Santa Cruz, CA, USA), 4-hydroxynonenal (4-HNE; Abcam), galectin-3 (Abcam), α-smooth muscle actin (α-SMA; Sigma-Aldrich), or collagen I (Abcam) overnight at 4 • C and then probed with a secondary antibody for 30 min at room temperature.…”

Section: Histology and Immunohistochemistry (Ihc)mentioning

confidence: 99%

Protective Effects of Melatonin Against Aristolochic Acid-Induced Nephropathy in Mice

2019

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Melatonin, a pineal hormone, is well known to regulate the sleep-wake cycle. Besides, the hormone has been shown to display pleiotropic effects arising from its powerful anti-oxidant and anti-inflammatory activities. Recent studies have reported that melatonin exerts protective effects in animal models of kidney disease. However, the potential effects of melatonin on aristolochic acid (AA)-induced nephropathy (AAN) have not yet been investigated. Here, we found that the administration of melatonin ameliorated AA-induced renal dysfunction, as evidenced by decreased plasma levels of blood urea nitrogen and creatinine and histopathological abnormalities such as tubular dilatation and cast formation. The upregulation of tubular injury markers after AA injection was reversed by melatonin. Melatonin also suppressed AA-induced oxidative stress, as evidenced by the downregulation of 4-hydroxynonenal and reduced level of malondialdehyde, and modulated expression of pro-oxidant and antioxidant enzymes. In addition, p53-dependent apoptosis of tubular epithelial cells, infiltration of macrophages and CD4 + T cells into damaged kidneys, and renal expression of cytokines and chemokines were inhibited by melatonin. Moreover, melatonin attenuated AA-induced tubulointerstitial fibrosis through suppression of the tumor growth factor-β/Smad signaling pathway. These results suggest that melatonin might be a potential therapeutic agent for AAN.

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Section: Histology and Immunohistochemistry (Ihc)mentioning

confidence: 99%

Protective Effects of Melatonin Against Aristolochic Acid-Induced Nephropathy in Mice

2019

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“…Here, we investigated the role of SIRT1 from a new perspective. SIRT1 is a key molecule involved in kidney injury (Kim et al, 2019;Zhang et al, 2019). Our study provides both in vitro and in vivo evidence to show that SIRT1 expression is upregulated in damaged tubular cells during cisplatin-induced AKI.…”

Section: Discussionmentioning

confidence: 66%

“…rhFGF21 Upregulates SIRT1 Expression in Renal Tubular Cells in vivo and in vitro SIRT1 is a key player in cisplatin-induced AKI and nephrotoxicity (Kim et al, 2019;Zhang et al, 2019). In cisplatin-treated HK-2 cells, SIRT1 protein levels were upregulated, similarly to FGF21 (Figures 5A,B).…”

Section: Cisplatin Induces a Significant Upregulation Of Fgf21 In Renmentioning

confidence: 90%

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SIRT1 Mediates Effects of FGF21 to Ameliorate Cisplatin-Induced Acute Kidney Injury

Chen

Yang

et al. 2020

Front. Pharmacol.

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Acute kidney injury (AKI) is a common complication in cancer patients. Kidney function is closely related to patients' quality of life and tumor prognosis. Cisplatin is a highly effective anti-tumor drug. However, the use of cisplatin is limited by its nephrotoxicity. It has been reported that FGF21 has a renal-protective function, but the mechanisms by which it does so remain unclear. In this study, we show that the expression of FGF21 is significantly upregulated in both in vitro and in vivo cisplatin-induced AKI models. Administration of recombinant FGF21 to cisplatin-induced AKI mice resulted in significantly decreased blood urea nitrogen (BUN) and serum creatinine levels, as well as significantly reduced protein levels of kidney injury molecule-1 (TIM-1), C-caspase 3, and Bax. H&E-stained kidney sections from cisplatin-induced AKI mice treated with recombinant FGF21 showed a relatively normal renal tissue structure, a reduced number of necrotic sites and vacuolar changes, and decreased casts, suggesting alleviated renal tubular injury. Experiments with an AKI cell model (cisplatin-treated HK-2 cells) yielded similar results as the mouse model; recombinant FGF21 significantly downregulated protein expression levels of TIM-1, C-caspase 3, and Bax. Furthermore, administration of recombinant FGF21 to cisplatin-treated AKI models significantly increased SIRT1 expression, and the beneficial effects of FGF21 on kidney injury were reversed by SIRT1 knockdown. Collectively, our results suggest that SIRT1 mediates the protective effect of FGF21 on cisplatin-induced kidney injury.

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“…inhibitor [35,36], followed by Western blotting analysis. As shown in Figure 5A, CTRP3 over-expression significantly suppressed the phosphorylation of NF-κB p65 and the acetylation of p53, whereas EX527 reversed the inhibitory effects of CTRP3 over-expression on NF-κB and p53 signaling in primary pancreatic acinar cells.…”

Section: Ctrp3 Regulates P53 and Nf-κb Signaling Pathways Via Sirt1 Imentioning

confidence: 99%

CTRP3 ameliorates cerulein-induced severe acute pancreatitis in mice via SIRT1/NF-κB/p53 axis

Wei

et al. 2020

Bioscience Reports

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Severe acute pancreatitis (SAP) is a common and life-threatening clinical acute abdominal disease. C1q/tumor necrosis factor-related protein 3 (CTRP3), a novel paralog of adiponectin, has been identified as a crucial regulator in multiple types of inflammatory disorders. However, the biological role of CTRP3 in SAP remains poorly understood. This study aimed to characterize the role of CTRP3 in SAP and illuminate the potential mechanisms involved. In the current study, SAP mouse models were induced by seven hourly intraperitoneal injection of cerulein (50 μg/kg) and an immediate intraperitoneal injection of lipopolysaccharide (10 mg/kg) after the last cerulein administration. Histological examination and serological analysis demonstrated that SAP mouse models were successfully established. Herein, we found that CTRP3 expression was significantly decreased in the pancreatic tissues of SAP mice compared with normal control mice. Furthermore, we explored the effects of CTRP3 rescue in SAP mice and discovered that CTRP3 over-expression attenuated pathological lesions, inhibited inflammatory mediator release and repressed acinar cell apoptosis. Notably, mechanistic studies revealed that CTRP3 over-expression suppressed NF-κB p65 phosphorylation and p53 acetylation to alleviate cerulein-induced SAP in mouse models through activation of silent information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent protein deacetylase. Collectively, our data indicate that CTRP3 may exert its protective effects in SAP mice via regulation of SIRT1-mediated NF-κB and p53 signaling pathways, implying a promising therapeutic strategy against SAP.

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Pharmacological Activation of Sirt1 Ameliorates Cisplatin-Induced Acute Kidney Injury by Suppressing Apoptosis, Oxidative Stress, and Inflammation in Mice

Cited by 58 publications

References 43 publications

Protective Effects of Melatonin Against Aristolochic Acid-Induced Nephropathy in Mice

Protective Effects of Melatonin Against Aristolochic Acid-Induced Nephropathy in Mice

SIRT1 Mediates Effects of FGF21 to Ameliorate Cisplatin-Induced Acute Kidney Injury

CTRP3 ameliorates cerulein-induced severe acute pancreatitis in mice via SIRT1/NF-κB/p53 axis

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