SIRT1–SIRT7 in Diabetic Kidney Disease: Biological Functions and Molecular Mechanisms

Frontiers in Endocrinology, Год журнала: 2022, Номер 13

Опубликована: Май 13, 2022

Diabetic kidney disease (DKD) is a severe microvascular complication in patients with diabetes and one of the main causes renal failure. The current clinical treatment methods for DKD are not completely effective, further exploration molecular mechanisms underlying pathology necessary to improve promote strategy. Sirtuins class III histone deacetylases, which play an important role many biological functions, including DNA repair, apoptosis, cell cycle, oxidative stress, mitochondrial function, energy metabolism, lifespan, aging. In last decade, research on sirtuins has gained increasing attention, it summarize relationship between increase awareness cure rates. We have found that miRNAs, lncRNAs, compounds, or drugs up-regulate activity expression protective roles function. Therefore, this review, we targets, mechanisms, signaling pathways SIRT1-SIRT7 models. Existing shown potential as effective targets DKD. This review aims lay solid foundation provide theoretical basis slow development patients.

Язык: Английский

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Lysophosphatidic Acid Induces Podocyte Pyroptosis in Diabetic Nephropathy by an Increase of Egr1 Expression via Downregulation of EzH2

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(12), С. 9968 - 9968

Опубликована: Июнь 9, 2023

Podocyte damage and renal inflammation are the main features pathogenesis of diabetic nephropathy (DN). Inhibition lysophosphatidic acid (LPA) receptor 1 (LPAR1) suppresses glomerular improves DN. Herein, we investigated LPA-induced podocyte its underlying mechanisms in We effects AM095, a specific LPAR1 inhibitor, on podocytes from streptozotocin (STZ)-induced mice. E11 cells were treated with LPA presence or absence expression NLRP3 inflammasome factors pyroptosis measured. A chromatin immunoprecipitation assay Western blotting performed to elucidate molecular mechanisms. Gene knockdown by transfecting small interfering RNA was used determine role transcription factor Egr1 (early growth response protein 1) histone methyltransferase EzH2 (Enhancer Zeste Homolog 2) injury. AM095 administration inhibited loss, expression, cell death STZ-induced In cells, increased activation via LPAR1. mediated LPA-treated cells. decreased H3K27me3 enrichment at promoter downregulating expression. further mice, suppressed increase EzH2/H3K27me3 reduction. Collectively, these results demonstrate that induces upregulating resulting pyroptosis, which may be potential mechanism DN progression.

Язык: Английский

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RIPK3 causes mitochondrial dysfunction and albuminuria in diabetic podocytopathy through PGAM5-Drp1 signaling

Metabolism, Год журнала: 2024, Номер 159, С. 155982 - 155982

Опубликована: Июль 30, 2024

Язык: Английский

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Mitochondria-associated endoplasmic reticulum membranes promote mitochondrial fission through AKAP1-Drp1 pathway in podocytes under high glucose conditions

Experimental Cell Research, Год журнала: 2023, Номер 424(2), С. 113512 - 113512

Опубликована: Фев. 10, 2023

Язык: Английский

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Combine Therapy of Gallic Acid and Allicin in Management of Diabetes

Journal for Research in Applied Sciences and Biotechnology, Год журнала: 2023, Номер 2(3), С. 91 - 99

Опубликована: Июнь 17, 2023

Type 2 diabetes, also known (DM) is a metabolic disorder with high mortality and disability incidence. The development activation of oxidative stress (OS) are crucial to the pathogenic DM. Pathophysiological evidence suggests that OS contributes onset progression DM through its association hyperglycemia, resistance insulin, inflammation. It's worth noting more studies investigating benefits natural antioxidants for managing Many different types culinary herbal plants contain antioxidant anti-inflammatory compounds gallic acid (GA) allicin, respectively. synthesis advanced glycation end products (AGEs) inhibited, fat stored less, blood sugar weight improved, body produces fewer AGEs, according study's authors. Inhibition RAGEs prevention AGE activity following treatment GA allicin resulted in reduced enhanced insulin secretion. goals this article (1) provide may be effective antihyperglycemic treatments complications (2) comprehensive review current state knowledge regarding examining role oleic disease.

Язык: Английский

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Regulation of autophagy by natural polyphenols in the treatment of diabetic kidney disease: therapeutic potential and mechanism

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Авг. 10, 2023

Diabetic kidney disease (DKD) is a major microvascular complication of diabetes and leading cause end-stage renal worldwide. Autophagy plays an important role in maintaining cellular homeostasis physiology. In DKD, the accumulation advanced glycation end products induces decreased autophagy-related protein expression transcription factor EB (TFEB) nuclear transfer, to impaired autophagy lysosomal function blockage autophagic flux. This accelerates resident cell injury apoptosis, mediates macrophage infiltration phenotypic changes, ultimately aggravated proteinuria fibrosis DKD. Natural polyphenols show promise treating DKD by regulating promoting transfer TFEB repair. review summarizes characteristics potential application mechanisms some known natural as regulators with goal contributing deeper understanding polyphenol treatment development their applications. Finally, we point out limitations current research provide outlook for future research.

Язык: Английский

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Integrative analysis of mitochondrial and immune pathways in diabetic kidney disease: identification of AASS and CASP3 as key predictors and therapeutic targets

Renal Failure, Год журнала: 2025, Номер 47(1)

Опубликована: Фев. 23, 2025

Objectives Diabetic kidney disease (DKD) is driven by mitochondrial dysfunction and immune dysregulation, yet the mechanistic interplay remains poorly defined. This study aimed to identify key molecular networks linking pathways DKD progression, with a focus on uncovering biomarkers therapeutic targets.

Язык: Английский

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Association of normal range of urinary albumin‐to‐creatinine ratio with all‐cause mortality among diabetic adults with preserved kidney function: National Health and Nutrition Examination Survey (NHANES) 2003–2018

Diabetes Obesity and Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Abstract Aim To ascertain the connection between normal‐range urinary albumin‐to‐creatinine ratio (UACR) and all‐cause mortality (ACM) among diabetic adults with preserved eGFR. Methods We used data from 2003–2018 National Health Nutrition Examination Survey. Nationally representative cross‐sectional survey linked outcomes Death Index. Restricted cubic spline curves (RCS) multivariable Cox regression models alongside subgroup analyses were utilised for estimating hazard ratios (HRs) 95% confidence intervals (Cls) UACR‐ACM interplay, adjusting demographic, socioeconomic, biochemical, medication medical history factors. The UACR's predictive accuracy survival was determined through receiver operating characteristic analysis. Results RCS analysis showcased that there no significant evidence to support a nonlinear relationship UACR ACM ( p = 0.080 nonlinearity) in participants diabetes mellitus (DM). In model 2 adjusted multiple confounding variables, HR 1.22 (95% CI, 1.06–1.40) per 10 mg/g raise continuous 1.50 (95%CI, 1.18–1.91) high tertile compared low. Kaplan–Meier showed significantly lower rates medium groups < 0.001). Subgroup manifested UACR–body mass index (BMI) interaction 0.033 interaction). Conclusions DM without overt kidney dysfunction, elevated independently related escalated ACM, particularly those normal BMI. conclude, we underscore significance of early risk assessment patients albuminuria, even dysfunction.

Язык: Английский

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Alstonia scholaris (L.) R. Br. ameliorated diabetic nephropathy through PPAR-δ pathway

Journal of Ethnopharmacology, Год журнала: 2025, Номер 348, С. 119839 - 119839

Опубликована: Апрель 26, 2025

Язык: Английский

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Activation of acetyl-CoA synthetase 2 mediates kidney injury in diabetic nephropathy

JCI Insight, Год журнала: 2023, Номер 8(20)

Опубликована: Окт. 22, 2023

Albuminuria and podocyte injury are the key cellular events in progression of diabetic nephropathy (DN). Acetyl-CoA synthetase 2 (ACSS2) is a nucleocytosolic enzyme responsible for regulation metabolic homeostasis mammalian cells. This study aimed to investigate possible roles ACSS2 kidney DN. We constructed an ACSS2-deleted mouse model role dysfunction models. In vitro, podocytes were chosen transfected with siRNA inhibitor treated high glucose. found that expression was significantly elevated patients DN mice. upregulation promoted phenotype transformation inflammatory cytokine while inhibiting podocytes' autophagy. Conversely, inhibition improved autophagy alleviated injury. Furthermore, epigenetically activated raptor by histone H3K9 acetylation, promoting activation target rapamycin complex 1 (mTORC1) pathway. Pharmacological or genetic depletion streptozotocin-induced greatly ameliorated dysfunction. To conclude, raptor/mTORC1-mediated inhibition.

Язык: Английский

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