Acta Diabetologica, Год журнала: 2025, Номер unknown
Опубликована: Июнь 5, 2025
Язык: Английский
Pharmacological Research, Год журнала: 2022, Номер 184, С. 106408 - 106408
Опубликована: Авг. 18, 2022
Язык: Английский
Процитировано
46
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
Процитировано
34
Cellular Signalling, Год журнала: 2024, Номер 118, С. 111144 - 111144
Опубликована: Март 15, 2024
Язык: Английский
Процитировано
10
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
Процитировано
10
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
Процитировано
39
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
Процитировано
20
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
Процитировано
1
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
Процитировано
1
Stem Cell Research & Therapy, Год журнала: 2025, Номер 16(1)
Опубликована: Март 18, 2025
Diabetic kidney disease (DKD) is the leading cause of end-stage renal (ESRD) globally, presenting a significant therapeutic challenge. Extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) have emerged as promising agents. This study explored effects and mechanisms EVs derived human placental (hP-MSCs) on DKD. were isolated cultured hP-MSCs administered to streptozotocin (STZ)-induced diabetic mice high glucose–treated glomerular mesangial cells. The impact was assessed through histological analysis biochemical assays. miR-99b-5p expression in its role modulating mechanistic target rapamycin (mTOR)/autophagy pathway examined via western blotting RT‒qPCR. Treatment with hP-MSC-derived significantly alleviated fibrosis improved function DKD models. These enriched miR-99b-5p, which targeted inhibited mTOR signaling, thereby increasing autophagic activity reducing cellular proliferation extracellular matrix accumulation tissues. can mitigate injury by miR-99b-5p/mTOR/autophagy pathway. findings suggest potential cell-free strategy for managing
Язык: Английский
Процитировано
1
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
Процитировано
16