Pathophysiologic mechanisms in diabetic kidney disease: A focus on current and future therapeutic targets

Diabetes Obesity and Metabolism, Journal Year: 2020, Volume and Issue: 22(S1), P. 16 - 31

Published: April 1, 2020

Abstract Diabetic kidney disease (DKD) is the primary cause of chronic around globe and one main complications in patients with type 1 2 diabetes. The standard treatment for DKD drugs controlling hyperglycemia high blood pressure. Renin angiotensin aldosterone system blockade sodium glucose cotransporter (SGLT2) inhibition have yielded promising results DKD, but many diabetic on such treatments nevertheless continue to develop leading failure cardiovascular comorbidities. New therapeutic options are urgently required. We review here avenues based insights into mechanisms that recently emerged, including mineralocorticoid receptor antagonists, SGLT2 inhibitors, glucagon‐like peptide‐1 agonist, endothelin A inhibition, anti‐inflammatory agents, autophagy activators epigenetic remodelling. involvement several molecular pathogenesis, together genetic variability this condition, makes it difficult target heterogeneous patient population a single drug. Personalized medicine, taking account mechanistic variability, may therefore improve renal protection DKD.

Language: Английский

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Renal and extrarenal regulation of body fluid composition

Elsevier eBooks, Journal Year: 2021, Volume and Issue: unknown, P. 411 - 443

Published: Nov. 12, 2021

Language: Английский

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Epigenetics in the pathogenesis of diabetic nephropathy

Acta Biochimica et Biophysica Sinica, Journal Year: 2021, Volume and Issue: 54(2), P. 163 - 172

Published: Dec. 23, 2021

Diabetic nephropathy (DN), which is a common microvascular complication with high incidence in diabetic patients, greatly increases the mortality of patients. With further study on DN, it found that epigenetics plays crucial role pathophysiological process DN. Epigenetics has an important impact development DN through variety mechanisms, and promotes generation maintenance metabolic memory, thus ultimately leading to poor prognosis. In this review we discuss methylation DNA, modification histone, regulation non-coding RNA involved progress cell dysfunction, inflammation fibrosis kidney, lead deterioration

Language: 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, 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

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Role of Pyroptosis in Diabetes and Its Therapeutic Implications

Journal of Inflammation Research, Journal Year: 2021, Volume and Issue: Volume 14, P. 2187 - 2206

Published: May 1, 2021

Pyroptosis is mainly considered as a new pro-inflammatory mediated-programmed cell death. In addition, pyroptosis described by gasdermin-induced pore formation on the membrane, swelling and rapid lysis, several mediators interleukin-1β (IL-1β) interleukin-18 (IL-18) release. Extensive studies have shown that commonly involved activating caspase-1-dependent canonical pathway caspase-4/5/11-dependent non-canonical pathway. However, facilitates local inflammation inflammatory responses. Current researches reported promotes progression of diabetic complications. Emerging suggested some potential molecules targeting inflammasome signaling pathways could be novel therapeutic avenue for managing treating diabetes its complications in near future. Our narrative review concisely describes possible mechanism progressive understanding development

Language: Английский

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Knockdown of LncRNA DLX6-AS1 inhibits HK-2 cell pyroptosis via regulating miR-223-3p/NLRP3 pathway in lipopolysaccharide-induced acute kidney injury

Journal of Bioenergetics and Biomembranes, Journal Year: 2020, Volume and Issue: 52(5), P. 367 - 376

Published: July 14, 2020

Language: Английский

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Non-Coding RNA and Diabetic Kidney Disease

DNA and Cell Biology, Journal Year: 2021, Volume and Issue: 40(4), P. 553 - 567

Published: March 18, 2021

Diabetic kidney disease (DKD) is one of the most common chronic microvascular complications diabetes. In addition to characteristic clinical manifestations proteinuria, it also has a complex pathological process that results from combined effects multiple factors involving whole renal structure such as glomeruli, tubules, and blood vessels. Non-coding RNAs (ncRNA) are transcripts with no or low coding potential, among which micro RNA (miRNA) been widely studied functional miRNA involved in regulation potential biomarker for prediction. The abundance long (lncRNA) vivo highly expressed certain degree research progress, but structural similarity makes still challenging. circular (circRNA) its early stages. It more relevant study provide link between diseases other tissues organs. This classification review mainly summarized biogenesis characteristics, mechanism ncRNA-regulating diseases, ways ncRNA prediction biomarker, interaction networks ncRNA.

Language: Английский

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Long non-coding RNA DLX6-AS1 is the key mediator of glomerular podocyte injury and albuminuria in diabetic nephropathy by targeting the miR-346/GSK-3β signaling pathway

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

Published: Feb. 28, 2023

Progressive albuminuria is the primary clinical symptom of diabetic nephropathy (DN), leading to a gradual decline in kidney function. DLX6-AS1 was first reported long non-coding RNA (lncRNA) participate organogenesis and play crucial roles brain or neural cell development. Herein, we investigated (Dlx6-os1 mice) role DN pathogenesis. We found that expression patients correlated with extent albuminuria. Dlx6-os1 overexpression induced cellular damage inflammatory responses cultured podocytes through miR-346-mediated regulation GSK-3β pathway. In various established newly developed knockout mouse models, knockdown/knockout significantly reduced podocyte injury The effects were remarkably modulated by miR-346 mimics mutants diminished podocyte-specific GSK-3β-knockout mice. Thus, (Dlx6-os1) promotes development accelerating inflammation upregulation pathway, providing novel molecular target for therapy.

Language: Английский

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Exploring the Therapeutic Significance of microRNAs and lncRNAs in Kidney Diseases

Genes, Journal Year: 2024, Volume and Issue: 15(1), P. 123 - 123

Published: Jan. 19, 2024

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two crucial classes of transcripts that belong to the major group (ncRNAs). These RNA molecules have significant influence over diverse molecular processes due their role as regulators gene expression. However, dysregulated expression these ncRNAs constitutes a fundamental factor in etiology progression wide variety multifaceted human diseases, including kidney diseases. In this context, past years, compelling evidence has shown miRNAs lncRNAs could be prospective targets for development next-generation drugs against diseases they participate number disease-associated processes, such podocyte nephron death, renal fibrosis, inflammation, transition from acute injury chronic disease, vascular changes, sepsis, pyroptosis, apoptosis. Hence, current review, we critically analyze recent findings concerning therapeutic inferences pathophysiological context Additionally, with aim driving advances formulation ncRNA-based tailored management discuss some key challenges future prospects should addressed forthcoming investigations.

Language: Английский

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Mesenchymal Stem Cell Derived Extracellular Vesicles Ameliorate Kidney Injury in Aristolochic Acid Nephropathy

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: March 24, 2020

Limitations in the current therapeutic strategies for prevention of progression chronic kidney disease (CKD) to end stage renal has been a drawback improving patient recovery. It is therefore imperative that solution found alleviate this problem and improve health well-being patients overall. Aristolochic acid (AA) induced nephropathy, type nephrotoxic CKD characterised by cortical tubular injury, inflammation, leading interstitial fibrosis. Extracellular vesicles derived from human bone marrow mesenchymal stem cells (MSC-EVs) display properties various models including injury. In study, we intended investigate ability MSC-EVs on ameliorating injury fibrosis mouse model aristolochic nephropathy (AAN). The AAN comprised an intraperitoneal injection AA NSG mice, followed three-day incubation period then inoculation intravenously. This routine was performed weekly basis four consecutive weeks, accompanied monitoring body weight all mice. Blood tissue samples were collected post sacrifice. All animals administered with developed A gradual loss observed, together deterioration function. Although no significant recovery observed following treatment MSC-EVs, reduction in: blood creatinine urea nitrogen (BUN), necrosis, observed. addition, infiltration CD45 positive immune cells, fibroblasts, pericytes which elevated interstitium also significantly reduced MSC-EVs. Kidneys subjected molecular analyses evaluate regulation pro-fibrotic genes. induction genes α-Sma, Tgfb1 Col1a1. downregulation fibroblasts activated injured mTECs vitro. Furthermore, meta-analyses miRNAs downregulated such as miR21, revealed multiple pathways involved fibrosis, apoptosis. These results suggest could play regenerative anti-fibrotic role through transfer biologically active cargo regulates both at protein genetic level.

Language: Английский

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