Long Non-Coding RNAs in the Pathogenesis of Diabetic Kidney Disease DOI Creative Commons

Mengsi Hu,

Qiqi Ma, Bing Liu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: April 20, 2022

Diabetic kidney disease (DKD) is one of the major microvascular complications diabetes mellitus, with relatively high morbidity and mortality globally but still in short therapeutic options. Over decades, a large body data has demonstrated that oxidative stress, inflammatory responses, hemodynamic disorders might exert critical influence initiation development DKD, whereas delicate pathogenesis DKD remains profoundly elusive. Recently, long non-coding RNAs (lncRNAs), extensively studied field cancer, are attracting increasing attentions on mellitus its including diabetic retinopathy, cardiomyopathy. In this review, we chiefly focused abnormal expression function lncRNAs resident cells (mesangial cell, endothelial podocyte, tubular epithelial cell) kidney, summarized roles elaborated their potential significance, order to advance our knowledge field, which help future research clinical treatment for disease.

Language: Английский

Autophagy-nutrient sensing pathways in diabetic complications DOI

Urvi M. Parmar,

Manjiri P. Jalgaonkar,

Yogesh A. Kulkarni

et al.

Pharmacological Research, Journal Year: 2022, Volume and Issue: 184, P. 106408 - 106408

Published: Aug. 18, 2022

Language: Английский

Citations

45
Autophagy and its therapeutic potential in diabetic nephropathy DOI Creative Commons

Yu-Peng Han,

Lijuan Liu,

Jia-Lin Yan

et al.

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

Citations

33
The regulatory role of miRNA and lncRNA on autophagy in diabetic nephropathy DOI
Siming Yu, Yue Li, Xinxin Lu

et al.

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

Published: March 15, 2024

Language: Английский

Citations

10
A systematic review of epigenetic interplay in kidney diseases: Crosstalk between long noncoding RNAs and methylation, acetylation of chromatin and histone DOI Open Access

Ruizhi Tan,

Jian Jia,

Tong Li

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116922 - 116922

Published: June 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.

Language: Английский

Citations

9
O-linked β-N-acetylglucosamine transferase regulates macrophage polarization in diabetic periodontitis: In vivo and in vitro study DOI Open Access

Yeke Wu,

Min Liu,

Hongling Zhou

et al.

World Journal of Diabetes, Journal Year: 2025, Volume and Issue: 16(3)

Published: Jan. 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

Language: Английский

Citations

1
α-methyltryptophan-mediated protection against diabetic nephropathy in db/db mice as studied with a metabolomics approach DOI Creative Commons

Aimin Cai,

Dan Shen,

Qiushuang Xiong

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 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.

Language: Английский

Citations

1
Down-regulation of Risa improves podocyte injury by enhancing autophagy in diabetic nephropathy DOI Creative Commons

Pei-Pei Su,

Dongwei Liu, Sijie Zhou

et al.

Military Medical Research, Journal Year: 2022, Volume and Issue: 9(1)

Published: May 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

Language: Английский

Citations

38
Autophagy and mitophagy: physiological implications in kidney inflammation and diseases DOI
Divya Bhatia, Mary E. Choi

AJP Renal Physiology, Journal Year: 2023, Volume and Issue: 325(1), P. F1 - F21

Published: May 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.

Language: Английский

Citations

19
Chinese herbal medicine and its active compounds in attenuating renal injury via regulating autophagy in diabetic kidney disease DOI Creative Commons
Peng Liu, Wenhui Zhu, Yang Wang

et al.

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

Published: March 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

Language: Английский

Citations

16
Macrophages communicate with mesangial cells through the CXCL12/DPP4 axis in lupus nephritis pathogenesis DOI Creative Commons
Weiwei Li,

Chun Yao,

Haixia Guo

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(5)

Published: May 18, 2024

Abstract Lupus nephritis (LN) occurs in 50% of cases systemic lupus erythematosus (SLE) and is one the most serious complications that can occur during progression. Mesangial cells (MCs) are intrinsic kidney regulate capillary blood flow, phagocytose apoptotic cells, secrete vasoactive substances growth factors. Previous studies have shown various types inflammatory activate MCs for hyperproliferation, leading to disruption filtration barrier impairment renal function LN. Here, we characterized heterogeneity LN mice by single-nucleus RNA sequencing (snRNA-seq) revealed interaction between macrophages through CXC motif chemokine ligand 12 (CXCL12)/dipeptidyl peptidase 4 (DPP4) axis. In culture, modulated proliferation migration this ligand–receptor interaction. mice, treatment with linagliptin, a DPP4 inhibitor, effectively inhibited MC reduced urinary protein levels. Together, our findings indicated targeting CXCL12/DPP4 axis linagliptin may serve as novel strategy via

Language: Английский

Citations

6