Autophagy-nutrient sensing pathways in diabetic complications

Pharmacological Research, Год журнала: 2022, Номер 184, С. 106408 - 106408

Опубликована: Авг. 18, 2022

Язык: Английский

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Autophagy and its therapeutic potential in diabetic nephropathy

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Март 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

Язык: Английский

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

Cellular Signalling, Год журнала: 2024, Номер 118, С. 111144 - 111144

Опубликована: Март 15, 2024

Язык: Английский

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A systematic review of epigenetic interplay in kidney diseases: Crosstalk between long noncoding RNAs and methylation, acetylation of chromatin and histone

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 176, С. 116922 - 116922

Опубликована: Июнь 13, 2024

The intricate crosstalk between long noncoding RNAs (lncRNAs) and epigenetic modifications such as chromatin/histone methylation acetylation offer new perspectives on the pathogenesis treatment of kidney diseases. lncRNAs, a class transcripts longer than 200 nucleotides with no protein-coding potential, are now recognized key regulatory molecules influencing gene expression through diverse mechanisms. They modulate by recruiting or blocking enzymes responsible for adding removing methyl acetyl groups, DNA, N6-methyladenosine (m6A) histone acetylation, subsequently altering chromatin structure accessibility. In diseases acute injury (AKI), chronic disease (CKD), diabetic nephropathy (DN), glomerulonephritis (GN), renal cell carcinoma (RCC), aberrant patterns DNA/RNA/histone have been associated onset progression, revealing complex interplay lncRNA dynamics. Recent studies highlighted how lncRNAs can impact pathology affecting function genes involved in cycle control, fibrosis, inflammatory responses. This review will separately address roles diseases, particular emphasis elucidating bidirectional effects underlying mechanisms conjunction addition to potential exacerbating renoprotective pathologies. Understanding reciprocal relationships not only shed light molecular underpinnings pathologies but also present avenues therapeutic interventions biomarker development, advancing precision medicine nephrology.

Язык: Английский

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α-methyltryptophan-mediated protection against diabetic nephropathy in db/db mice as studied with a metabolomics approach

Frontiers in Pharmacology, Год журнала: 2025, Номер 15

Опубликована: Янв. 20, 2025

Introduction Diabetic nephropathy (DN), a major complication of diabetes, presents with poor clinical outcomes and affects patients throughout their lifetime. α-Methyltryptophan (α-MT) is blocker the amino acid transporter. SLC6A14 also an inhibitor indoleamine 2,3-dioxygenase-1 (IDO1). Methods In this study, we employed nuclear magnetic resonance-based metabolomic approach to investigate therapeutic effects α-MT in db/db mouse model DN explore underlying molecular mechanisms. Results The results study demonstrated that significantly reduced urinary excretion albumin creatinine, improved kidney function, decreased renal fibrosis mice. Metabolomic analyses tissues urine samples indicated mice displayed increased activity enzyme IDO1, alongside pronounced metabolic disturbances. These disturbances are chiefly characterized by alterations metabolism, energy production pathways, membrane biochemical features, nicotinamide all which have been implicated mTOR signaling apoptotic pathways. Discussion Administration showed evidence IDO1 inhibition rectification dysfunctions concurrent suppression apoptosis. findings highlight potential as promising agent for diabetic nephropathy.

Язык: Английский

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Down-regulation of Risa improves podocyte injury by enhancing autophagy in diabetic nephropathy

Military Medical Research, Год журнала: 2022, Номер 9(1)

Опубликована: Май 26, 2022

Abstract Background LncRNA AK044604 (regulator of insulin sensitivity and autophagy, Risa ) autophagy-related factors Sirt1 GSK3β play important roles in diabetic nephropathy (DN). In this study, we sought to explore the effect on Sirt1/GSK3β-induced podocyte injury. Methods Diabetic db/db mice received -inhibition adeno-associated virus (AAV) via tail vein injection, intraperitoneal injection lithium chloride (LiCl). Blood, urine, kidney tissue samples were collected analyzed at different time points. Immortalized mouse cells (MPCs) cultured treated with lentivirus (LV), EX-527, LiCl. MPCs under stimulations as noted. The effects autophagy examined by qRT-PCR, Western blotting analysis, transmission electron microscopy, Periodic Acid-Schiff staining, immunofluorescence staining. Results activated overexpressed, but was downregulated DN high glucose-treated ( P < 0.001, db/m vs. db/db, NG or HM HG), which correlated poor prognosis. overexpression attenuated Sirt1-mediated downstream levels aggravated injury inhibiting expression HG). contrast, suppression enhanced Sirt1-induced injury, could be abrogated EX-527 + -AAV HG -LV Furthermore, LiCl treatment restore GSK3β-mediated podocytes suggesting that decreasing autophagy. Conclusion inhibit regulating Sirt1/GSK3β axis, thereby aggravating DN. may serve a therapeutic target for

Язык: Английский

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Autophagy and mitophagy: physiological implications in kidney inflammation and diseases

AJP Renal Physiology, Год журнала: 2023, Номер 325(1), С. F1 - F21

Опубликована: Май 11, 2023

Autophagy is a ubiquitous intracellular cytoprotective quality control program that maintains cellular homeostasis by recycling superfluous cytoplasmic components (lipid droplets, protein, or glycogen aggregates) and invading pathogens. Mitophagy selective form of autophagy damaged mitochondrial material, which can extracellularly act as damage-associated molecular patterns, prevents their release. mitophagy are indispensable for the maintenance kidney exert crucial functions during both physiological disease conditions. Impaired negatively impact pathophysiological state promote its progression. helps in maintaining structural integrity kidney. Mitophagy-mediated explicitly critical regulating Both attenuate inflammatory responses An accumulating body evidence highlights persistent injury-induced oxidative stress contribute to dysregulated autophagic mitophagic cell death. also communicate with programmed death pathways (apoptosis necroptosis) play important roles survival preventing nutrient deprivation stress. activated after acute injury. However, aberrant hyperactivation be deleterious cause tissue damage. The findings on various models chronic heterogeneous type- context-specific dependent. In this review, we discuss pathological manifestations.

Язык: Английский

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O-linked β-N-acetylglucosamine transferase regulates macrophage polarization in diabetic periodontitis: In vivo and in vitro study

World Journal of Diabetes, Год журнала: 2025, Номер 16(3)

Опубликована: Янв. 20, 2025

BACKGROUND Periodontitis, when exacerbated by diabetes, is characterized increased M1 macrophage polarization and decreased M2 polarization. O-linked β-N-acetylglucosamine (O-GlcNAcylation), catalyzed O-GlcNAc transferase (OGT), promotes inflammatory responses in diabetic periodontitis (DP). Additionally, p38 mitogen-activated protein kinase regulates However, the interplay between OGT, polarization, signaling progression of DP remains unexplored. AIM To investigate effect OGT on its role mediating O-GlcNAcylation p38. METHODS For vivo experiments, mice were divided into four groups: Control, model, model + short hairpin (sh) RNA-negative control, sh-OGT. Diabetes was induced streptozotocin, followed ligation lipopolysaccharide (LPS) administration to induce periodontitis. The impact assessed injecting sh-OGT lentivirus. Maxillary bone destruction evaluated using micro-computed tomography analysis tartrate-resistant acid phosphatase staining, while determined through quantitative real-time polymerase chain reaction (qPCR) immunohistochemistry. vitro RAW264.7 cells treated with LPS high glucose (HG) (25 mmol/L D-glucose) establish a cell DP. inhibited inhibitor (OSMI4) treatment knocked down transfection. M1/M2 analyzed qPCR, immunofluorescence, flow cytometry. Levels measured immunoprecipitation western blotting. RESULTS Our results demonstrated that led maxillary loss mice, associated elevated levels. Knockdown promoted shift from both mouse periodontal tissues HG-induced cells. Furthermore, HG enhanced interacted promote at residues A28, T241, T347, as well phosphorylation residue Y221. CONCLUSION Inhibition OGT-mediated deactivates pathway suppressing self-phosphorylation, thereby promoting mitigating These findings suggested modulating regulation may represent novel therapeutic strategy for treating

Язык: Английский

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Chinese herbal medicine and its active compounds in attenuating renal injury via regulating autophagy in diabetic kidney disease

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Март 3, 2023

Diabetic kidney disease (DKD) is the main cause of end-stage renal worldwide, and there a lack effective treatment strategies. Autophagy highly conserved lysosomal degradation process that maintains homeostasis energy balance by removing protein aggregates damaged organelles. Increasing evidence suggests dysregulated autophagy may contribute to glomerular tubulointerstitial lesions in under diabetic conditions. Emerging studies have shown Chinese herbal medicine its active compounds ameliorate injury regulating autophagy. In this review, we summarize dysregulation or insufficiency cells, including podocytes, mesangial proximal tubular epithelial key mechanism for development DKD, focus on protective effects compounds. Moreover, systematically reviewed DKD regulated herb compound preparations, single compounds, so as provide new drug candidates clinical DKD. Finally, also candidate targets Therefore, further research with regulation their great significance realization targeted therapies

Язык: Английский

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Artesunate Alleviates Kidney Fibrosis in Type 1 Diabetes with Periodontitis Rats via Promoting Autophagy and Suppression of Inflammation

ACS Omega, Год журнала: 2024, Номер 9(14), С. 16358 - 16373

Опубликована: Март 29, 2024

To explore the effect of periodontal disease on progression diabetic kidney (DKD), to observe effects artesunate (ART) intervention and tissues in type 1 rats with periodontitis, possibility ART for treatment DKD. Rat models diabetes mellitus, mellitus periodontitis were established through streptozotocin (STZ) intraperitoneal injection, maxillary first molar ligation, P. gingivalis ligation applied sequentially. Ten weeks after modeling, gavage was given 4 weeks. Immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot used investigate inflammatory factors, fibrogenisis, autophagy-related proteins tissues, 16S rDNA sequencing detect changes dental plaque fluid tissue flora. Compared control group, protein expression levels transforming growth factor β1 (TGF-β1) COL-IV (PD) group increased. The TGF-β1, Smad3, increased DM + PD upregulated group. These results suggest that enhances renal fibrosis this process is related TGF-β1/Smad/COL-IV signaling pathway. Among top five dominant bacteria abundance Proteobacteria most significantly, followed by Actinobacteria Firmicutes mild increases. relative Proteobacteria, Actinobacteria, groups also showed an increasing trend compared CON trend, which may mediate increase oxidative stress promote occurrence development DN. Periodontal lead imbalance flora, aggravate damage T1DM, cause glomerular inflammation tubulointerstitial fibrosis, reduce level autophagy. delays inhibiting TGF-β-Smad

Язык: Английский

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