Deletion of soluble epoxide hydrolase suppressed chronic kidney disease-related vascular calcification by restoring Sirtuin 3 expression

He, Wanbing; Huang, Jieping; Yang, Liu; Xie, Changming; Zhang, Kun; Zhu, Xinhong; Chen, Jie; Huang, Hui

doi:10.1038/s41419-021-04283-6

Cited by 16 publications

(13 citation statements)

References 27 publications

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“…One of the important functions of sEH is metabolizing epoxyeicosatrienoic acids (EETs), which is an anti-inflammatory substant. Based on the protective properties of EETs, inhibition of sHE is a potential target for kidney protection ( Manhiani et al, 2009 ; Greite et al, 2020 ; Lin et al, 2020 ; He et al, 2021 ). However, the exact functions of six RFRGs in the kidney still need further study.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Network-Based Analyses Reveal Novel Renal Function-Related Targets in Acute Kidney Injury

Zhang

Cai

et al. 2022

Front. Genet.

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Background: Acute kidney injury (AKI) is a common clinical syndrome with limited methods of treatment and diagnosis. Although several molecules associated with AKI have been discovered, molecular mechanisms underlying AKI still remain unclear. Weighted gene co-expression network analysis (WGCNA) is a novel method to uncover the relationship between co-expression genes and clinical traits at the system level.Methods: First, by employing WGCNA in transcriptional data on 30 patients with well/poor functioning kidney graft, we identified two co-expression modules that were significantly related to serum creatinine (SCr). Second, based on the modules, potential small molecular compound candidates for developing targeted therapeutics were obtained by connectivity map analysis. Furthermore, multiple validations of expression in space/time were carried out with two classical AKI models in vivo and other five databases of over 152 samples.Results: Two of the 14 modules were found to be closely correlated with SCr. Function enrichment analysis illustrated that one module was enriched in the immune system, while the other was in the metabolic process. Six key renal function-related genes (RFRGs) were finally obtained. Such genes performed well in cisplatin-induced or cecal ligation and puncture-induced AKI mouse models.Conclusion: The analysis suggests that WGCNA is a proper method to connect clinical traits with genome data to find novel targets in AKI. The kidney tissue with worse renal function tended to develop a “high immune but low metabolic activity” expression pattern. Also, ACSM2A, GLYAT, CORO1A, DPEP1, ALDH7A1, and EPHX2 are potential targets of molecular diagnosis and treatment in AKI.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Network-Based Analyses Reveal Novel Renal Function-Related Targets in Acute Kidney Injury

Zhang

Cai

et al. 2022

Front. Genet.

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“…Pathogenesis of vascular calcification is complex. Recent studies on vascular imaging, cell biology, and molecular biology have suggested that vascular calcification is a cell-mediated active and highly controllable biological process [ 26 ]. CAC promotes cardiovascular event occurrence and development [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of C1q/TNF-Related Protein 9 on Coronary Artery Calcification: An Observational Study

Liu

Ying

Jin

et al. 2022

JCDD

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Coronary artery calcification (CAC) increases the risk of acute coronary syndrome. This study examined the correlation between C1q/TNF-related protein 9 (CTRP9) and CAC and explored CTRP9 as a biomarker for prognosis. We divided 275 patients with coronary heart disease into four groups. In order to balance the baseline confounding factors, propensity score matching (PSM) was performed to match CAC patients with non-CAC patients in a 1:1 ratio. Optical coherence tomography (OCT) calcification scoring was performed in 126 patients with CAC. Moreover, 140 patients who underwent OCT were followed-up for 9 months for analysis of the correlation between CTRP9 levels and clinical prognosis. Based on OCT calcification scores, 126 patients with CAC were divided into the 0–2 and 3–4 groups. Plasma CTRP9 levels were significantly lower in the type 2 diabetes mellitus (T2DM), CAC and CAC with T2DM groups than in the control group. CTRP9 played roles as a protective factor and potential predictor in CAC severity. The AUC of the OCT calcification score 3–4 group predicted by the plasma CTRP9 level was 0.766. During the follow-up period, the cumulative event-free survival rate was significantly lower in the low-level CTRP9 (L-CTRP9) group than in the high-level (H-CTRP9) group, and the incidence of major endpoint events was significantly higher in the L-CTRP9 group than in the H-CTRP9 group. CTRP9 can be a valuable biomarker for CAC occurrence and severity and can predict patients’ clinical prognosis.

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“…Downregulation of SIRT3 might induce an increase in the acetylation of PGC-1α, leading to PGC-1α dysfunction, which also compromised mitochondrial adenosine triphosphate (ATP) production and morphology damage, ultimately triggering VSMCs phenotypic transition and calcium deposition. Furthermore, deletion of soluble epoxide hydrolase was reported to stabilize and increase SIRT3, thereby ameliorating mitochondrial abnormalities and VC in CKD or high phosphate conditions ( 78 ). Currently, berberine, honokiol, and resveratrol have been confirmed to target SIRT3 to correct pathological condition.…”

Section: Sirtuins and Vascular Calcificationmentioning

confidence: 99%

The Role of Sirtuins in Osteogenic Differentiation of Vascular Smooth Muscle Cells and Vascular Calcification

Wang

2022

Front. Cardiovasc. Med.

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Vascular calcification (VC) is a common pathological change in many chronic diseases, such as diabetes and chronic kidney disease. It is mainly deposited in the intima and media of vessels in the form of hydroxyapatite. Recently, a lot of research has been performed to show that VC is associated with various cellular stresses, such as hyperphosphate, hyperglycemia and oxidative stress. Unfortunately, our understanding of the pathogenesis of calcification is far from comprehensive. Sirtuins belong to a family of class III highly conserved deacetylases that are involved in the regulation of biological and cellular processes including mitochondrial biogenesis, metabolism, oxidative stress, inflammatory response, DNA repair, etc. Numerous studies have shown that sirtuins might play protective roles in VC, and restoring the activity of sirtuins may be a potentially effective treatment for VC. However, the exact mechanism of their vascular protection remains unclear. Here, we reviewed the roles of sirtuins in the osteogenic transformation of vascular smooth muscle cells and the development of VC. We also elucidated the applications of sirtuins agonists for the treatment of VC.

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Deletion of soluble epoxide hydrolase suppressed chronic kidney disease-related vascular calcification by restoring Sirtuin 3 expression

Cited by 16 publications

References 27 publications

Comprehensive Network-Based Analyses Reveal Novel Renal Function-Related Targets in Acute Kidney Injury

Comprehensive Network-Based Analyses Reveal Novel Renal Function-Related Targets in Acute Kidney Injury

Effect of C1q/TNF-Related Protein 9 on Coronary Artery Calcification: An Observational Study

The Role of Sirtuins in Osteogenic Differentiation of Vascular Smooth Muscle Cells and Vascular Calcification

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