Development of Biomarkers and Molecular Therapy Based on Inflammatory Genes in Diabetic Nephropathy

Maiti, Amit K

doi:10.3390/ijms22189985

Cited by 19 publications

(13 citation statements)

References 125 publications

(129 reference statements)

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“…This can be the foremost common complication for proteinuric and non-proteinuric end-stage renal disease (ESRD) [ 2 ]. This condition eventually ends up in diabetic kidney disease (DKD) which may be a leading reason for morbidity in chronic nephropathy which is chronic kidney disease (CKD) [ 3 ]. A collection of physiological dysfunctions known as diabetes mellitus (DM) is characterized by persistent hyperglycemia.…”

Section: Introductionmentioning

confidence: 99%

A Narrative Review of New Treatment Options for Diabetic Nephropathy

Pillai¹,

Fulmali²

2023

Cureus

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Diabetic nephropathy (DN) is a type of nephropathy that is caused by a diabetic condition. Diabetic nephropathy is seen in type 1 and type 2 diabetes. End-stage renal disorders are brought on by DN. Diabetic nephropathy is thought to be linked to metabolic changes in the body. Proteinuria and glomerular filtration rate are the two most crucial diagnostic and prognosis measures for diabetic kidney disease (DKD), yet both have significant disadvantages. Novel biomarkers are thus increasingly required to improve risk factors and detect disease at an early stage. Controlling blood glucose and vital sign like body temperature and blood pressure, reducing cholesterol levels, and blocking the renin-angiotensin system are the standard treatments for diabetic patients. On the other hand, if used too late within the course of the disease, these therapeutic techniques can only provide partial relief from nephropathy.The complicated pathophysiology of the diabetic kidney, which experiences a variety of severe structural, metabolic, and functional alterations, represents one of the most important obstacles to the event of effective therapeutics for DN. Despite these issues, new diabetes models have identified promising treatment targets by identifying the mechanisms that control important functions of podocytes and glomerular endothelial cells. It has been shown in the vast majority of trials that renin-angiotensin system inhibitors combined with integrative therapies work well for DN. Combining sodium-glucose cotransporter-2 inhibitors and renin-angiotensin-aldosterone system blockers is a novel way to slow down the course of DKD by lowering inflammatory and fibrotic indicators brought on by hyperglycemia, which is more effective than using either medicine alone. Aldosterone receptor inhibitors and advanced glycation end-product inhibitors are two recently produced medications that may be used successfully to treat DN.

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Section: Introductionmentioning

confidence: 99%

A Narrative Review of New Treatment Options for Diabetic Nephropathy

Pillai¹,

Fulmali²

2023

Cureus

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“…Diabetes is a chronic metabolic disorder characterized by hyperglycemia. It affects the kidneys and tubules, leading to debilitating end-stage renal disease and diabetic nephropathy (DN) (Bonnet and Scheen, 2018;Maiti, 2021;Cefalu et al, 2016). Diabetes, characteristic of high blood sugar, mainly includes type 1, type 2, and monogenic and fibrocalculous pancreatic diabetes (Bloomgarden, 2016;Vendhan et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

An integrated bioinformatics analysis and experimental study identified key biomarkers CD300A or CXCL1, pathways and immune infiltration in diabetic nephropathy mice

LIANG¹,

Luo²,

ZHANG³

et al. 2022

Biocell

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Diabetic nephropathy (DN) is a common microvascular complication that easily leads to end-stage renal disease. It is important to explore the key biomarkers and molecular mechanisms relevant to diabetic nephropathy (DN). We used highthroughput RNA sequencing to obtain the genes related to DN glomerular tissues and healthy glomerular tissues of mice.Then we used LIMMA to analyze differentially expressed genes (DEGs) between DN and non-diabetic glomerular samples. And we performed KEGG, gene ontology functional (GO) enrichment, and gene set enrichment analysis to reveal the signaling pathway of the disease. The CIBERSORT algorithm based on support vector machine was used to determine the immune infiltration score. Random forest algorithm and Cytoscape obtained hub genes. Finally, we applied co-staining, immunohistochemical staining, RT-qPCR and western blotting to validate the protein and mRNA expression of both hub genes. We obtained 913 DEGs mainly related to inflammatory factors and immunity. GSEA results showed that differential genes were mainly enriched in IL-17 signaling pathway, lipid and atherosclerosis, rheumatoid arthritis, TNF signaling pathway, neutrophil extracellular trap formation, Staphylococcus aureus infection and other pathways. The intersection of the random forest algorithm and Cytoscape revealed both hub genes of CD300A and CXCL1. Experiments have shown that the both key genes of CD300A and CXCL1 shown increased expression in glomerular podocytes, and are related to the inflammation of diabetic nephropathy. And immunohistochemical staining and RT-qPCR further confirmed that the protein and mRNA expression level of CD300A or CXCL1 in glomeruli tissue in DN mice were increased. The expression levels of CD300A and CXCL1 increased significantly under HG (high glucose) stimulation, further confirming that diabetes can lead to increased levels of CD300A and CXCL1 at the cellular level. Through bioinformatics analysis, machine learning algorithms, and experimental research, CD300A and CXCL1 are confirmed as both potential biomarkers in diabetic nephropathy. And we further revealed the main pathways of differential genes and the differentially distributed immune infiltrating cells in diabetic nephropathy.

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“…The occurrence of DN can induce a series of abnormal changes such as glomerular hypertrophy, podocyte loss, and mesangial matrix expansion ( Alicic et al, 2017 ). Progressive DN is not only the result of glucose metabolism disorder and reactive oxygen species (ROS) production, but also the result of chronic low-grade inflammation and fibrosis ( Rayego-Mateos et al, 2020 ; Maiti, 2021 ). Genomics analysis found significant ferroptosis in the DN group ( Wang et al, 2022c ).…”

Section: Introductionmentioning

confidence: 99%

NLRP3-mediated pyroptosis in diabetic nephropathy

Wan

Pan

et al. 2022

Front. Pharmacol.

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Diabetic nephropathy (DN) is the main cause of end-stage renal disease (ESRD), which is characterized by a series of abnormal changes such as glomerulosclerosis, podocyte loss, renal tubular atrophy and excessive deposition of extracellular matrix. Simultaneously, the occurrence of inflammatory reaction can promote the aggravation of DN-induced kidney injury. The most important processes in the canonical inflammasome pathway are inflammasome activation and membrane pore formation mediated by gasdermin family. Converging studies shows that pyroptosis can occur in renal intrinsic cells and participate in the development of DN, and its activation mechanism involves a variety of signaling pathways. Meanwhile, the activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome can not only lead to the occurrence of inflammatory response, but also induce pyroptosis. In addition, a number of drugs targeting pyroptosis-associated proteins have been shown to have potential for treating DN. Consequently, the pathogenesis of pyroptosis and several possible activation pathways of NLRP3 inflammasome were reviewed, and the potential drugs used to treat pyroptosis in DN were summarized in this review. Although relevant studies are still not thorough and comprehensive, these findings still have certain reference value for the understanding, treatment and prognosis of DN.

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Development of Biomarkers and Molecular Therapy Based on Inflammatory Genes in Diabetic Nephropathy

Cited by 19 publications

References 125 publications

A Narrative Review of New Treatment Options for Diabetic Nephropathy

A Narrative Review of New Treatment Options for Diabetic Nephropathy

An integrated bioinformatics analysis and experimental study identified key biomarkers CD300A or CXCL1, pathways and immune infiltration in diabetic nephropathy mice

NLRP3-mediated pyroptosis in diabetic nephropathy

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