Pathophysiologic Mechanisms and Potential Biomarkers in Diabetic Kidney Disease

Diabetes & Metabolism Journal, Journal Year: 2022, Volume and Issue: 46(2), P. 181 - 197

Published: March 25, 2022

Although diabetic kidney disease (DKD) remains the leading cause of end-stage eventually requiring chronic replacement therapy, prevalence DKD has failed to decline over past 30 years. In order reduce prevalence, extensive research been ongoing improve prediction onset and progression. most commonly used markers are albuminuria estimated glomerular filtration rate, their limitations have encouraged researchers search for novel biomarkers that could risk stratification. Considering is a complex process involves several pathophysiologic mechanisms such as hyperglycemia induced inflammation, oxidative stress, tubular damage, damage fibrosis, many capture one specific mechanism developed. Moreover, increasing use high-throughput omic approaches analyze biological samples include proteomics, metabolomics, transcriptomics emerged strong tool in biomarker discovery. This review will first describe recent advances understanding pathophysiology DKD, second, current clinical well status multiple potential with respect protein biomarkers, transcriptomics.

Language: Английский

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Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives

Biomolecules, Journal Year: 2022, Volume and Issue: 12(9), P. 1227 - 1227

Published: Sept. 2, 2022

Diabetes mellitus (DM) is one of the most debilitating chronic diseases worldwide, with increased prevalence and incidence. In addition to its macrovascular damage, through microvascular complications, such as Diabetic Kidney Disease (DKD), DM further compounds quality life these patients. Considering DKD main cause end-stage renal disease (ESRD) in developed countries, extensive research currently investigating matrix pathophysiology. Hyperglycemia, inflammation oxidative stress (OS) are mechanisms behind this disease. By generating pro-inflammatory factors (e.g., IL-1,6,18, TNF-α, TGF-β, NF-κB, MCP-1, VCAM-1, ICAM-1) activation diverse pathways PKC, ROCK, AGE/RAGE, JAK-STAT), they promote a pro-oxidant state impairment antioxidant system (NRF2/KEAP1/ARE pathway) and, finally, alterations filtration unit. Hitherto, wide spectrum pre-clinical clinical studies shows beneficial use NRF2-inducing strategies, NRF2 activators Bardoxolone methyl, Curcumin, Sulforaphane their analogues), other natural properties treatment. However, limitations regarding lack larger trials, solubility or delivery hamper implementation for use. Therefore, review, we will discuss mechanisms, especially NRF2/KEAP1/ARE involvement, while highlighting potential therapeutic approaches that target via OS.

Language: Английский

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REDD1 expression in podocytes facilitates renal inflammation and pyroptosis in streptozotocin-induced diabetic nephropathy

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 7, 2025

Abstract Sterile inflammation resulting in an altered immune response is a key determinant of renal injury diabetic nephropathy (DN). In this investigation, we evaluated the hypothesis that hyperglycemic conditions augment pro-inflammatory kidney by promoting podocyte-specific expression stress protein regulated development and DNA damage 1 (REDD1). support hypothesis, streptozotocin (STZ)-induced diabetes increased REDD1 abundance concomitant with cell infiltration. mice, administration SGLT2 inhibitor dapagliflozin was followed reductions blood glucose concentration, abundance, contrast +/+ −/− mice did not exhibit albuminuria, factors, or macrophage cultured human podocytes, exposure to promoted REDD1-dependent activation NF-κB signaling. deletion podocytes attenuated both increase chemokine chemotaxis under conditions. Notably, prevented infiltration kidneys mice. Furthermore, pyroptotic death, evidenced NLRP3-mediated caspase-1 activity LDH release. also required for pyroptosis markers glomeruli The data necessary chronic context raises prospect therapies targeting may be helpful DN.

Language: Английский

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HIF-α Prolyl Hydroxylase Inhibitors and Their Implications for Biomedicine: A Comprehensive Review

Biomedicines, Journal Year: 2021, Volume and Issue: 9(5), P. 468 - 468

Published: April 24, 2021

Oxygen is essential for the maintenance of body. Living organisms have evolved systems to secure an oxygen environment be proper. Hypoxia-inducible factor (HIF) plays role in this process; it a transcription that mediates erythropoietin (EPO) induction at transcriptional level under hypoxic environment. After successful cDNA cloning 1995, line studies were conducted elucidating molecular mechanism HIF activation response hypoxia. In 2001, dioxygenases acting on prolines and asparagine residues, which play roles process, was reported. HIF-prolyl hydroxylases (PHs) are molecules constitute core detecting decrease partial pressure oxygen, or hypoxia, cells; they can called sensors. review, I discuss process HIF-PH, explains hypoxia-induced EPO expression; development HIF-PH inhibitors artificially exogenously activate by inhibiting HIF-PH; significance implications medical intervention using inhibitors.

Language: Английский

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What’s New in the Molecular Mechanisms of Diabetic Kidney Disease: Recent Advances

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 24(1), P. 570 - 570

Published: Dec. 29, 2022

Diabetic kidney disease (DKD) is the leading cause of chronic disease, including end-stage and increases risk cardiovascular mortality. Although treatment options for DKD, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, sodium-glucose cotransporter 2 mineralocorticoid antagonists, have advanced, their efficacy still limited. Thus, a deeper understanding molecular mechanisms DKD onset progression necessary development new innovative treatments DKD. The complex pathogenesis includes various different pathways, can be broadly classified into inflammatory, fibrotic, metabolic, hemodynamic factors. Here, we summarize recent findings in basic research, focusing on each factor advances Collective evidence from clinical research studies helpful definitive regulatory systems. Further comprehensive exploration warranted to advance our knowledge establish novel preventive strategies.

Language: Английский

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GLP-1 receptor agonists in diabetic kidney disease: current evidence and future directions

Kidney Research and Clinical Practice, Journal Year: 2022, Volume and Issue: 41(2), P. 136 - 149

Published: March 25, 2022

With the emergence of various classes blood glucose-lowering agents, choosing appropriate drug for each patient is emphasized in diabetes management. Among incretin-based drugs, glucagon-like peptide 1 (GLP-1) receptor agonists are a promising therapeutic option patients with diabetic kidney disease (DKD). Several cardiovascular outcome trials have demonstrated that GLP-1 beneficial effects on cardiorenal outcomes beyond their type 2 mellitus (T2DM). The renal protective likely result from direct actions kidney, addition to indirect improve conventional risk factors DKD, such as reducing glucose levels, pressure, and body weight. Inhibition oxidative stress inflammation induction natriuresis major renoprotective mechanisms analogues. Early evidence development dual triple combination agents suggests will probably become popular treatment options T2DM.

Language: Английский

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Role of Natural and Synthetic Compounds in Modulating NRF2/KEAP1 Signaling Pathway in Prostate Cancer

Cancers, Journal Year: 2023, Volume and Issue: 15(11), P. 3037 - 3037

Published: June 2, 2023

Prostate cancer is the second most common in men worldwide. can be treated by surgery or active surveillance when early diagnosed but, at an advanced metastatic stage, radiation therapy androgen-deprivation needed to reduce progression. However, both of these therapies cause prostate resistance treatment. Several studies demonstrated that oxidative stress involved occurrence, development, progression and treatment resistance. The nuclear factor erythroid 2-related 2 (NRF2)/KEAP1 (Kelch-Like ECH-Associated Protein 1) pathway plays important role protecting cells against damage. Reactive oxygen species (ROS) levels NRF2 activation determine cell fate. In particular, toxic ROS lead physiological death tumor suppression, while lower are associated with carcinogenesis On contrary, a high level promotes survival related activating adaptive antioxidant response. this review, we analyzed current literature regarding natural synthetic compounds modulating NRF2/KEAP1 signaling cancer.

Language: Английский

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Heart failure with preserved ejection fraction (HFpEF) in type 2 diabetes mellitus: from pathophysiology to therapeutics

Journal of Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 14(5)

Published: April 29, 2022

Type 2 diabetes mellitus (T2DM or T2D) is a devastating metabolic abnormality featured by insulin resistance, hyperglycemia, and hyperlipidemia. T2D provokes unique changes compromises cardiovascular geometry function. Meanwhile, increases the overall risk for heart failure (HF) acts independent of classical factors including coronary artery disease, hypertension, valvular diseases. The incidence HF extremely high in patients with manifested as preserved, reduced, midrange ejection fraction (HFpEF, HFrEF, HFmrEF, respectively), all which significantly worsen prognosis T2D. HFpEF seen approximately half cases defined heterogenous syndrome discrete phenotypes, particularly close association syndrome. Nonetheless, management remains unclear, largely due to poorly pathophysiology behind HFpEF. Here, this review, we will summarize findings from multiple preclinical clinical studies well recent trials, mainly focusing on pathophysiology, potential mechanisms, therapies

Language: Английский

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Astragalus membranaceus and Salvia miltiorrhiza ameliorate diabetic kidney disease via the “gut-kidney axis”

Phytomedicine, Journal Year: 2023, Volume and Issue: 121, P. 155129 - 155129

Published: Sept. 29, 2023

Language: Английский

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Klotho’s impact on diabetic nephropathy and its emerging connection to diabetic retinopathy

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

Published: April 18, 2023

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide and a significant burden on healthcare systems. α-klotho (klotho) protein known for its anti-aging properties has been shown to delay onset age-related diseases. Soluble klotho produced by cleavage full-length transmembrane disintegrin metalloproteases, it exerts various physiological effects circulating throughout body. In type 2 diabetes complications DN, decrease in expression observed. This reduction levels may indicate progression DN suggest that be involved multiple pathological mechanisms contribute development DN. article examines potential soluble as therapeutic agent with focus ability impact pathways. These pathways include anti-inflammatory oxidative stress, anti-fibrotic, endothelial protection, prevention vascular calcification, regulation metabolism, maintenance calcium phosphate homeostasis, cell fate through modulation autophagy, apoptosis, pyroptosis retinopathy shares similar targeting offer new insights into treatment both conditions. Finally, this review assesses drugs used clinical practice modulate different their improve impacting levels.

Language: Английский

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