Autophagy and its therapeutic potential in diabetic nephropathy

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: March 20, 2023

Diabetic nephropathy (DN), the leading cause of end-stage renal disease, is most significant microvascular complication diabetes and poses a severe public health concern due to lack effective clinical treatments. Autophagy lysosomal process that degrades damaged proteins organelles preserve cellular homeostasis. Emerging studies have shown disorder in autophagy results accumulation diabetic cells promotes development DN. regulated by nutrient-sensing pathways including AMPK, mTOR, Sirt1, several intracellular stress signaling such as oxidative endoplasmic reticulum stress. An abnormal nutritional status excess stresses caused diabetes-related metabolic disorders disturb autophagic flux, dysfunction Here, we summarized role DN focusing on modulate therapeutic interferences

Language: Английский

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Crosstalk between proximal tubular epithelial cells and other interstitial cells in tubulointerstitial fibrosis after renal injury

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

The energy needs of tubular epithelial components, especially proximal cells (PTECs), are high and they heavily depend on aerobic metabolism. As a result, particularly vulnerable to various injuries caused by factors such as ischemia, proteinuria, toxins, elevated glucose levels. Initial metabolic phenotypic changes in PTECs after injury likely an attempt at survival repair. Nevertheless, cases recurrent or prolonged injury, have the potential undergo transition secretory state, leading generation discharge diverse bioactive substances, including transforming growth factor-β, Wnt ligands, hepatocyte factor, interleukin (IL)-1β, lactic acid, exosomes, extracellular vesicles. By promoting fibroblast activation, macrophage recruitment, endothelial cell loss, these compounds stimulate communication between other interstitial cells, ultimately worsening renal damage. This review provides summary latest findings that facilitate cellular categories, advancement tubulointerstitial fibrosis (TIF).

Language: Английский

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The regulatory role of miRNA and lncRNA on autophagy in diabetic nephropathy

Cellular Signalling, Journal Year: 2024, Volume and Issue: 118, P. 111144 - 111144

Published: March 15, 2024

Language: Английский

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M1-derived extracellular vesicles polarize recipient macrophages into M2-like macrophages and alter skeletal muscle homeostasis in a hyper-glucose environment

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 27, 2024

Abstract Background Macrophages release not only cytokines but also extracellular vesicles (EVs). which are small membrane-derived nanovesicles with virus-like properties transferring cellular material between cells. Until now, the consequences of macrophage plasticity on and composition EVs have been poorly explored. In this study, we determined impact high-glucose (HG) concentrations metabolism, characterized their derived-EV subpopulations. Finally, whether HG-treated macrophage-derived participate in immune responses metabolic alterations skeletal muscle Methods THP1-macrophages were treated 15mM (MG15) or 30mM (MG30) glucose. Then, M1/M2 canonical markers, pro- anti-inflammatory cytokines, activities proteins involved glycolysis oxidative phosphorylation evaluated. Macrophage-derived by TEM, NTA, MRSP, 1 H-Nuclear magnetic resonance spectroscopy for lipid composition. C2C12 cells used as recipients MG15 MG30-derived EVs. The profiles recipient determined, well mRNA levels relevant genes polarization metabolism. Results Untreated macrophages released large (sEVs, lEVs) different distributions. Proportionally to glucose concentration, was induced macrophages, associated mitochondrial dysfunction, triacylglycerol cholesterol accumulation. addition, MG30 had increased level CD86 increase pro-inflammatory cytokines. HG affected sphingolipid phospholipid compositions. differences sEVs lEVs abolished reflected macrophages. Interestingly, expression CD163, Il-10 contents insulin-induced AKT hyper-phosphorylation accumulation myotubes, a state observed pre-diabetes. Conversely, insulin-resistance myotubes. Conclusions As inflammation involves first M1 then activation M2 resolve inflammation, study demonstrates that dialog through EV route is an intrinsic part inflammatory response. hyperglycemic context, could development chronic inflammation.

Language: Английский

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Circulating non-coding RNAs in chronic kidney disease and its complications

Nature Reviews Nephrology, Journal Year: 2023, Volume and Issue: 19(9), P. 573 - 586

Published: June 7, 2023

Language: Английский

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The Role of Immune Cells in DKD: Mechanisms and Targeted Therapies

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 2103 - 2118

Published: April 1, 2024

Diabetic kidney disease (DKD), is a common microvascular complication and major cause of death in patients with diabetes.Disorders immune cells cytokines can accelerate DKD development number ways.As the composed complex highly differentiated cells, interactions among different cell types play important regulatory roles development.Here, we summarize latest research into molecular mechanisms underlying various renal DKD.In addition, discuss most recent studies related to single technology bioinformatics analysis field DKD.The aims our review were explore as potential therapeutic targets provide some guidance for future clinical treatments.

Language: Английский

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Frontier role of extracellular vesicles in kidney disease

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 20, 2024

Language: Английский

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Identification of a novel immune landscape signature as effective diagnostic markers related to immune cell infiltration in diabetic nephropathy

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 8, 2023

Background The study aimed to identify core biomarkers related diagnosis and immune microenvironment regulation explore the molecular mechanism of diabetic nephropathy (DN) through bioinformatics analysis. Methods GSE30529, GSE99325, GSE104954 were merged with removing batch effects, different expression genes (DEGs) screened at a criterion |log2FC| >0.5 adjusted P <0.05. KEGG, GO, GSEA analyses performed. Hub by conducting PPI networks calculating node using five algorithms CytoHubba, followed LASSO ROC analysis accurately diagnostic biomarkers. In addition, two GEO datasets, GSE175759 GSE47184, an experiment cohort 30 controls 40 DN patients detected IHC, used validate Moreover, ssGSEA was performed analyze in DN. Wilcoxon test regression determine signatures. correlation between crucial signatures calculated Spearman Finally, cMap potential drugs treating renal tubule injury patients. Results A total 509 DEGs, including 338 upregulated 171 downregulated genes, out. “chemokine signaling pathway” “cell adhesion molecules” enriched both KEGG CCR2, CX3CR1, SELP, especially for combination model three identified as high capabilities striking AUC, sensitivity, specificity validated datasets IHC validation. Immune infiltration showed notable advantage APC co-stimulation, CD8+ T cells, checkpoint, cytolytic activity, macrophages, MHC class I, parainflammation group. that SELP strongly positively correlated dilazep out underlying compound analyzed CMap. Conclusions are DN, their combination. may participate occurrence development At last, be promising drug

Language: Английский

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Relationship between Macrophages and Tissue Microenvironments in Diabetic Kidneys

Biomedicines, Journal Year: 2023, Volume and Issue: 11(7), P. 1889 - 1889

Published: July 3, 2023

Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease. Increasing evidence has suggested that inflammation a key microenvironment involved in development and progression DN. Studies have confirmed macrophage accumulation closely related to human Macrophage phenotype highly regulated by surrounding diabetic kidneys. M1 M2 macrophages represent distinct sometimes coexisting functional phenotypes same population, with their roles implicated pathological changes, such as fibrosis associated stage Recent findings from single-cell RNA sequencing DN further heterogeneity plasticity macrophages. In addition, intrinsic renal cells interact directly or through changes tissue microenvironment. depletion, modification its polarization, autophagy could be potential new therapies for

Language: 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, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 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.

Language: Английский

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