Podocyte Death in Diabetic Kidney Disease: Potential Molecular Mechanisms and Therapeutic Targets

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 9035 - 9035

Опубликована: Авг. 20, 2024

Cell deaths maintain the normal function of tissues and organs. In pathological conditions, abnormal activation or disruption cell death often leads to pathophysiological effects. Diabetic kidney disease (DKD), a significant microvascular complication diabetes, is linked high mortality morbidity rates, imposing substantial burden on global healthcare systems economies. Loss detachment podocytes are key changes in progression DKD. This review explores potential mechanisms apoptosis, necrosis, autophagy, pyroptosis, ferroptosis, cuproptosis, podoptosis podocytes, focusing how different modes contribute It recognizes limitations current research presents latest basic clinical studies targeting podocyte pathways Lastly, it focuses future treat DKD, with intention inspiring further development therapeutic strategies.

Язык: Английский

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Inhibition of complement system-related gene ITGB2 attenuates epithelial–mesenchymal transition and inflammation in diabetic nephropathy

European journal of medical research, Год журнала: 2025, Номер 30(1)

Опубликована: Фев. 8, 2025

Emerging evidences have indicated a role of the complement system in pathogenesis diabetic nephropathy (DN). Thus, this study was conducted to explore system-related key biomarkers for patients with DN. DN microarray datasets were downloaded from GEO database, followed by differentially expressed genes (DEGs) screening. Complement (CSRGs) searched various databases. Weighted Gene Co-expression Network Analysis (WGCNA) employed screen DN-related genes, then differential CSRGs (DCSRGs) identified, protein–protein interaction (PPI) network construction. In addition, acquired two machine learning algorithms, immune infiltration analysis, Set Enrichment (GSEA), and potential drugs screening conducted. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) western blotting utilized detect ITGB2 expression. Then cell viability, inflammatory factors, expression epithelial–mesenchymal transition (EMT) fibrosis markers determined using Cell Counting Kit-8 (CCK-8) assay, enzyme linked immunosorbent assay (ELISA), assays, respectively. total, 1012 DEGs 974 screened, intersection analysis three (DN-related CSRGs) yielded 13 which considered as DCSRGs. Subsequently, 2 identified learning, namely VWF ITGB2. The both enriched pathways chemokine signaling pathway, CAMs, focal adhesion natural killer cell-mediated cytotoxicity, significantly correlated activated mast cells, resting NK macrophages. Also, related clinical features, including age, serum creatinine level, GFR (MDRD). Besides, mRNA protein levels HG-treated HK-2 cells remarkably elevated. Moreover, viability TNF-α, IL-6, IL-12, α-SMA, E-cadherin vimentin changed HG administration reversed ITGB2-silence. gene overexpressed DN, inhibition attenuated EMT inflammation

Язык: Английский

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ZHX2 inhibits diabetes-induced liver injury and ferroptosis by epigenetic silence of YTHDF2

Nutrition and Diabetes, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 22, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common complication of type 2 diabetes mellitus (DM). The transcription factor zinc fingers and homeoboxes (ZHX2) has been implicated in the pathogenesis chronic diseases, yet its precise role underlying mechanism DM-induced hepatic injury remain poorly elucidated. To investigate this, we used high-fat diet (HFD) streptozotocin (STZ) administration to create DM model mice, while high glucose (HG) exposure was simulate vitro. Through various experiments such as luciferase reporter assay, chromatin immunoprecipitation, RNA rescue experiments, aimed uncover mechanisms involving ZHX2. Our findings revealed that ZHX2 lower YTHDF2 higher livers mice HG-induced Huh7 cells. overexpression rescued injury. also reversed ferroptosis vivo Mechanistically, recognized m6A-modified mRNA promoted degradation. In turn, inhibited by binding promoter region. Knockdown led increased cells through activating YTHDF2-induced GPX4 SLC7A11 These highlight involvement ZHX2-YTHDF2-ferroptosis pathway suggest targeting this may hold therapeutic potential for improving injuries.

Язык: Английский

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Irisin Is a Potential Novel Biomarker and Therapeutic Target Against Kidney Diseases

Cell Biochemistry and Function, Год журнала: 2025, Номер 43(5)

Опубликована: Май 1, 2025

ABSTRACT Kidney diseases, characterized by renal dysfunction, are the leading causes of death worldwide. It is crucial to prevent and treat kidney diseases reduce their associated morbidity mortality. Moderate physical exercise has been recognized be advantageous for health. Irisin an exercise‐induced myokine that was identified in 2012. plays important role energy bone metabolism, oxidative stress reduction, anti‐inflammatory processes, cell inhibition, cardiovascular protection. However, relationship between irisin have not fully elucidated. This review explores as a biomarker disease diagnosis its complications, well mechanisms through which it participates various pathways, such apoptosis, autophagy, pyroptosis, ferroptosis. Furthermore, secretion levels were discussed provide basis prevention treatment avenues, therapeutic guidance developing new promising intervention strategies. Clinical Trial Registration : None.

Язык: Английский

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The role of ferroptosis in acute kidney injury: mechanisms and potential therapeutic targets

Molecular and Cellular Biochemistry, Год журнала: 2024, Номер unknown

Опубликована: Июнь 28, 2024

Язык: Английский

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Metformin attenuates PM _2.5 -induced oxidative stress by inhibiting the AhR/CYP1A1 pathway in proximal renal tubular epithelial cells

Toxicology Mechanisms and Methods, Год журнала: 2024, Номер 34(9), С. 1022 - 1034

Опубликована: Июль 22, 2024

The harmful effects of PM

Язык: Английский

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Natural product Swietenine improve the progression of diabetic nephropathy by inhibiting ferroptosis through activation of the Akt/GSK-3β/Nrf2 signaling pathway

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Май 14, 2024

Background Ferroptosis is a newly defined form of iron dependent regulatory cell death distinct from apoptosis, autophagy, and necrosis, characterized by an abnormal increase in intracellular lipid reactive oxygen species. Diabetes nephropathy (DN) one the most common complications diabetes cause end-stage renal disease. Recent studies have shown that ferroptosis plays important role occurrence development diabetic nephropathy. Swietenine belongs to limonin class compounds, which are extracted Swietenia macrophylla King, plant genus Swietenia, family Meliaceae King not been artificially synthesized date. It natural product with variety pharmacological activities such as anti diabetes, improving inflammation, anti-oxidation, anti-bacterial, anti-tumor, etc. However, it unclear whether can improve inhibiting glomerular podocytes (MPC-5) its potential mechanism. Objective This study investigated Swi through Akt/GSK-3β/Nrf2 signaling pathway inhibits MPC-5 improves process diabetes. Method In vivo, 8-week-old SD rats were induced STZ/HFD investigate effect on DN resisting ferroptosis. vitro, inhibitory effects death. By giving verify activation related inhibitors downstream proteins. Results this study, treatment improved injury rats, was proved function indexes, histopathological parameters podocyte damage protein. addition, inhibited vivo. HG-induced viability, cells. activating pathway, promotes expression anti-ferroptosis Conclusion Our research findings suggest for first time may be new regulates thereby reducing level high glucose nephropathy, expected become promising candidate drug

Язык: Английский

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Human Umbilical Cord Mesenchymal Stem Cells Alleviate Diabetic Nephropathy by Inhibiting Ferroptosis via the JNK/KEAP1/NRF2 Signaling Pathway

Antioxidants and Redox Signaling, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 26, 2024

Diabetic nephropathy (DN) is a major cause of end-stage renal disease, with no therapeutic interventions available to control its progression. Ferroptosis, an iron-dependent regulated cell death characterized by lipid peroxidation, plays pivotal role in the pathogenesis DN. Human umbilical cord mesenchymal stem cells (hUCMSCs) are effective treatment modality for DN; however, underlying mechanism action remains unclear. The aim present study was investigate whether hUCMSCs alleviate DN via inhibiting ferroptosis and molecular mechanisms type 2 diabetic mice high-glucose palmitate-stimulated human tubular epithelial (HK-11) models.

Язык: Английский

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The association between vitamin D receptor gene polymorphism FokI and type 2 diabetic kidney disease and its molecular mechanism: a case control study

BMC Medical Genomics, Год журнала: 2024, Номер 17(1)

Опубликована: Дек. 18, 2024

Язык: Английский

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