Recent Advances in the Management of Diabetic Kidney Disease: Slowing Progression

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3086 - 3086

Published: March 7, 2024

Diabetic kidney disease (DKD) is a major cause of chronic (CKD), and it heightens the risk cardiovascular incidents. The pathogenesis DKD thought to involve hemodynamic, inflammatory, metabolic factors that converge on fibrotic pathway. Genetic predisposition unhealthy lifestyle practices both play significant role in development progression DKD. In spite recent emergence angiotensin receptors blockers (ARBs)/angiotensin converting enzyme inhibitor (ACEI), sodium-glucose cotransporter 2 (SGLT2) inhibitors, nonsteroidal mineralocorticoid antagonists (NS-MRAs), current therapies still fail effectively arrest Glucagon-like peptide 1 receptor agonists (GLP-1RAs), promising class agents, possess potential act as renal protectors, slowing Other including pentoxifylline (PTF), selonsertib, baricitinib hold great promise for due their anti-inflammatory antifibrotic properties. Multidisciplinary treatment, encompassing modifications drug therapy, can decelerate Based treatment heart failure, recommended use multiple drugs combination rather than single-use Unearthing mechanisms underlying urgent optimize management Inflammatory (including IL-1, MCP-1, MMP-9, CTGF, TNF-a TGF-β1), along with lncRNAs, not only serve diagnostic biomarkers, but also therapeutic targets. this review, we delve into We explore additional value combing these develop novel strategies. Drawing from understanding pathogenesis, propose HIF AGE epigenetic targets future.

Language: Английский

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Long noncoding RNA ENST00000436340 promotes podocyte injury in diabetic kidney disease by facilitating the association of PTBP1 with RAB3B

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(2)

Published: Feb. 15, 2023

Dysfunction of podocytes has been regarded as an important early pathologic characteristic diabetic kidney disease (DKD), but the regulatory role long noncoding RNAs (lncRNAs) in this process remains largely unknown. Here, we performed RNA sequencing tissues isolated from DKD patients and nondiabetic renal cancer undergoing surgical resection discovered that novel lncRNA ENST00000436340 was upregulated high glucose-induced podocytes, showed a significant correlation between injury. Gain- loss-of-function experiments silencing alleviated podocyte injury cytoskeleton rearrangement. Mechanistically, fat mass obesity- associate gene (FTO)-mediated m6A induced upregulation ENST00000436340. interacted with polypyrimidine tract binding protein 1 (PTBP1) augmented PTBP1 to RAB3B mRNA, promoted mRNA degradation, thereby caused rearrangement inhibition GLUT4 translocation plasma membrane, leading progression. Together, our results suggested could promote through PTBP1-dependent regulation, thus suggesting form lncRNA-mediated epigenetic regulation contributes pathogenesis DKD.

Language: Английский

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Long Non-Coding RNA NEAT1 Regulates Pyroptosis in Diabetic Nephropathy via Mediating the miR-34c/NLRP3 Axis

Kidney & Blood Pressure Research, Journal Year: 2020, Volume and Issue: 45(4), P. 589 - 602

Published: Jan. 1, 2020

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus and considered to be sterile inflammatory disease. Increasing evidence suggest that pyroptosis subsequent response play key role in the pathogenesis DN. However, underlying cellular molecular mechanisms responsible for DN are largely unknown.The rat models were successfully established by single 65 mg/kg streptozotocin treatment. Glomerular mesangial cells exposed 30 mmol/L high glucose media 48 h mimic environment vitro. Gene protein expressions determined quantitative real-time PCR Western blot. Cell viability measured MTT assay flow cytometry analysis, respectively. The relationship between lncRNA NEAT1, miR-34c, Nod-like receptor protein-3 (NLRP3) was confirmed luciferase reporter assay.We found upregulation NEAT1 associated with increase models. as target gene mediated effect on regulating expression NLRP3 well caspase-1 interleukin-1β. Either miR-34c inhibition or overexpression could reverse accentuation inflammation sh-NEAT1 transfection vitro model DN.Our findings suggested its regulated cell via mediating DN, providing new insights into understanding

Language: Английский

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Silencing of long noncoding RNA XIST protects against renal interstitial fibrosis in diabetic nephropathy via microRNA-93-5p-mediated inhibition of CDKN1A

AJP Renal Physiology, Journal Year: 2019, Volume and Issue: 317(5), P. F1350 - F1358

Published: Sept. 23, 2019

Long noncoding RNAs (lncRNAs) have been reported to play an important role in diabetic nephropathy (DN). However, the molecular mechanism involved this process remains poorly understood. Thus, present study aimed explore function and of dysregulated lncRNA X-inactive specific transcript (XIST) DN. DN mouse models were established by streptozotocin treatment, human renal tubular epithelial HK-2 cells exposed high glucose produce vitro model. XIST was highly expressed tissues patients with DN, mice glucose-exposed cells. To identify interaction among XIST, miR-93-5p, cyclin-dependent kinase inhibitor 1A (CDKN1A) analyze functional significance their interstitial fibrosis, we altered endogenous expression miR-93-5p CDKN1A. Dual-luciferase reporter assay results suggested that kidney tissue identified be a could bind CDKN1A target miR-93-5p. Downregulated led increase expression, thereby decreasing suppressing fibrosis Consistently, knockdown reduced markers (fibronectin, collagen type IV, transforming growth factor-β1). Restoration or yielded reversed effect on fibrosis. In conclusion, our demonstrated silenced inducing miR-93-5p-dependent inhibition beneficial for preventing which may provide future strategy prevent progression

Language: Английский

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LncRNA-antisense non-coding RNA in the INK4 locus promotes pyroptosis via miR-497/thioredoxin-interacting protein axis in diabetic nephropathy

Life Sciences, Journal Year: 2020, Volume and Issue: 264, P. 118728 - 118728

Published: Nov. 5, 2020

Language: Английский

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Non-Coding RNAs in IGF-1R Signaling Regulation: The Underlying Pathophysiological Link between Diabetes and Cancer

Cells, Journal Year: 2019, Volume and Issue: 8(12), P. 1638 - 1638

Published: Dec. 14, 2019

The intricate molecular network shared between diabetes mellitus (DM) and cancer has been broadly understood. DM associated with several hormone-dependent malignancies, including breast, pancreatic, colorectal (CRC). Insulin resistance, hyperglycemia, inflammation are the main pathophysiological mechanisms linking to cancer. Non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) long non-coding (lncRNAs), widely appreciated as pervasive regulators of gene expression, governing evolution metabolic disorders, ways ncRNAs affect development complicated have only started be revealed in recent years. Insulin-like growth factor 1 receptor (IGF-1R) signaling is a master regulator processes directing In this review, we briefly summarize number well-known miRNAs lncRNAs that regulate IGF-1R cancer, respectively, further discuss potential underlying pathogenesis disease association.

Language: Английский

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Role of long non‐coding RNAs in adipogenesis: State of the art and implications in obesity and obesity‐associated diseases

Obesity Reviews, Journal Year: 2021, Volume and Issue: 22(7)

Published: Jan. 14, 2021

Summary Obesity is an evolutionary, chronic, and relapsing disease that consists of a pathological accumulation adipose tissue able to increase morbidity for high blood pressure, type 2 diabetes, metabolic syndrome, obstructive sleep apnea in adults, children, adolescents. Despite intense research over the last 20 years, obesity remains today with complex multifactorial etiology. Recently, long non‐coding RNAs (lncRNAs) are emerging as interesting new regulators different lncRNAs have been found play role early late phases adipogenesis be implicated obesity‐associated complications onset. In this review, we discuss most recent advances on adipocyte biology complications. Indeed, more researchers focusing investigating underlying roles these molecular modulators could play. Even if significant number evidence correlation‐based, being differentially expressed specific disease, works now focused deeply analyzing how can effectively modulate pathogenesis onset progression. LncRNAs possibly represent markers useful future both diagnosis prompt clinical management patients obesity.

Language: Английский

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LncRNA lnc‐ISG20 promotes renal fibrosis in diabetic nephropathy by inducing AKT phosphorylation through miR‐486‐5p/NFAT5

Journal of Cellular and Molecular Medicine, Journal Year: 2021, Volume and Issue: 25(11), P. 4922 - 4937

Published: May 3, 2021

Abstract Long non‐coding RNA (lncRNA) lnc‐ISG20 has been found aberrantly up‐regulated in the glomerular patients with diabetic nephropathy (DN). We aimed to elucidate function and regulatory mechanism of lncRNA on DN‐induced renal fibrosis. Expression patterns kidney tissues DN were determined by RT‐qPCR. Mouse models constructed, while MCs cultured under normal glucose (NG)/high (HG) conditions. The expression fibrosis marker proteins collagen IV, fibronectin TGF‐β1 measured Western blot assay. In addition, relationship among lnc‐ISG20, miR‐486‐5p, NFAT5 AKT analysed using dual‐luciferase reporter assay immunoprecipitation. effect miR‐486/NFAT5/p‐AKT axis DN‐associated was also verified means rescue experiments. levels increased patients, mouse HG‐treated MCs. Lnc‐ISG20 silencing alleviated HG‐induced delayed mice. Mechanistically, miR‐486‐5p be a downstream miRNA inhibited binding its 3'UTR. overexpression aggravated stimulating phosphorylation. However, reversed promotion vitro vivo caused overexpression. Our collective findings indicate that promotes process activating through miR‐486‐5p/NFAT5 axis. High‐expression may useful indicator for DN.

Language: Английский

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RETRACTED: LNCRNA CDKN2B-AS1 regulates mesangial cell proliferation and extracellular matrix accumulation via miR-424-5p/HMGA2 axis

Biomedicine & Pharmacotherapy, Journal Year: 2019, Volume and Issue: 121, P. 109622 - 109622

Published: Nov. 25, 2019

Previous study has demonstrated that long noncoding RNA cyclin-dependent kinase inhibitor 2B antisense 1 (CDKN2B-AS1) was abnormally expressed in diabetic nephropathy (DN). However, the underlying mechanism allows CDKN2B-AS1 progression of DN remains to be further elucidated.Peripheral blood cells 24 diabetes patients with and 20 without were collected. Human glomerular mesangial (HGMC) cultured high glucose or low medium. The expression levels CDKN2B-AS1, microRNA (miR)-424-5p mobility group AT hook 2 (HMGA2) detected by quantitative real-time polymerase chain reaction western blot. target association between miR-424-5p HMGA2 confirmed dual-luciferase reporter immunoprecipitation assays. Cell proliferation, extracellular matrix (ECM) accumulation phosphatidylinositol 3-kinase (PI3K)/protein B (AKT) signaling investigated 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) blot, respectively.CDKN2B-AS1 up-regulated level down-regulated peripheral glucose-treated HGMC cells. validated as a sponge miR-424-5p. Silence repressed proliferation ECM increasing overexpression inhibited PI3K/AKT pathway targeting HMGA2. Moreover, knockdown miR-424-5p.Knockdown suppressed decreasing HMGC

Language: Английский

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LncRNA KCNQ1OT1 affects cell proliferation, apoptosis and fibrosis through regulating miR-18b-5p/SORBS2 axis and NF-ĸB pathway in diabetic nephropathy

Diabetology & Metabolic Syndrome, Journal Year: 2020, Volume and Issue: 12(1)

Published: Sept. 3, 2020

Abstract Background It has been reported that long non-coding RNAs (lncRNAs) play vital roles in diabetic nephropathy (DN). Our study aims to research the function of lncRNA KCNQ1OT1 DN cells and molecular mechanism. Methods Human glomerular mesangial (HGMCs) human renal endothelial (HRGECs) were cultured high glucose (30 mM) condition as models cells. KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) miR-18b-5p levels detected by quantitative real-time polymerase chain reaction (qRT-PCR). The mRNA protein Sorbin SH3 domain-containing 2 (SORBS2), Type IV collagen (Col-4), fibronectin (FN), transcriptional regulatory factor-beta (TGF-β1), Twist, NF-κB STAT3 measured qRT-PCR western blot. Cell viability was cell counting kit-8 (CCK-8) assay for selecting proper concentration treatment. Additionally, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) flow cytometry employed determine proliferation apoptosis, respectively. targets predicted online software confirmed dual-luciferase reporter assay. Results SORBS2 elevated DN. Both knockdown silencing restrained fibrosis induced apoptosis Besides, Overexpression restored knockdown-mediate effects on proliferation, In addition, served a target well targeted SORBS2. repressed NF-ĸB pathway. Conclusion regulated via KCNQ1OT1/miR-18b-5p/SORBS2 axis

Language: Английский

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