Effects of Disodium Cromoglycate Treatment in the Early Stage of Diabetic Nephropathy: Focus on Collagen Deposition

Luz, Mateus Jacinto da; Costa, Victor Augusto Alves da; Balbi, Ana Paula Coelho; Bispo-da-Silva, Luiz Borges

doi:10.1248/bpb.b21-00662

Cited by 1 publication

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References 22 publications

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“…Mast cell accumulation and degranulation levels were found elevated as the disease progresses of DN, which participated in tubulointerstitial injury through the production of tryptase, chymase, TGF-β1, renin, and TNF-α ( 33 ). Disodium cromoglycate could inhibit the degranulation of mast cells and lighten tubulointerstitial collagen deposition in rats with type I diabetes ( 34 ). Chymase inhibitor TY-51469 suppressed oxidative stress in the renal podocytes of diabetic db/db mice, thereby decreasing albuminuria ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

GBP2 promotes M1 macrophage polarization by activating the notch1 signaling pathway in diabetic nephropathy

Liu

et al. 2023

Front. Immunol.

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BackgroundDiabetic nephropathy (DN) is one of the most common diabetic complications, which has become the primary cause of end-stage renal disease (ESRD) globally. Macrophage infiltration has been proven vital in the occurrence and development of DN. This study was designed to investigate the hub genes involved in macrophage-mediated inflammation of DN via bioinformatics analysis and experimental validation.MethodsGene microarray datasets were obtained from the Gene Expression Omnibus (GEO) public website. Integrating the CIBERSORT, weighted gene co-expression network analysis (WGCNA) and DEGs, we screened macrophage M1-associated key genes with the highest intramodular connectivity. Subsequently, the Least Absolute Shrinkage and Selection Operator (LASSO) regression was utilized to further mine hub genes. GSE104954 acted as an external validation to predict the expression levels and diagnostic performance of these hub genes. The Nephroseq online platform was employed to evaluate the clinical implications of these hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to elucidate the dominant biological functions and signal pathways. Finally, we conducted experiments to verify the role of GBP2 in M1 macrophage-mediated inflammatory response and the underlying mechanism of this role.ResultsSixteen DEGs with the highest connectivity in M1 macrophages-associated module (paleturquoise module) were determined. Subsequently, we identified four hub genes through LASSO regression analysis, including CASP1, MS4A4A, CD53, and GBP2. Consistent with the training set, expression levels of these four hub genes manifested memorably elevated and the ROC curves indicated a good diagnostic accuracy with an area under the curve of greater than 0.8. Clinically, enhanced expression of these four hub genes predicted worse outcomes of DN patients. Given the known correlation between the first three hub genes and macrophage-mediated inflammation, experiments were performed to demonstrate the effect of GBP2, which proved that GBP2 contributed to M1 polarization of macrophages by activating the notch1 signaling pathway.ConclusionOur findings detected four hub genes, namely CASP1, MS4A4A, CD53, and GBP2, may involve in the progression of DN via pro-inflammatory M1 macrophage phenotype. GBP2 could be a promising prognostic biomarker and intervention target for DN by regulating M1 polarization.

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Section: Discussionmentioning

confidence: 99%

GBP2 promotes M1 macrophage polarization by activating the notch1 signaling pathway in diabetic nephropathy

Liu

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

show abstract

Effects of Disodium Cromoglycate Treatment in the Early Stage of Diabetic Nephropathy: Focus on Collagen Deposition

Cited by 1 publication

References 22 publications

GBP2 promotes M1 macrophage polarization by activating the notch1 signaling pathway in diabetic nephropathy

GBP2 promotes M1 macrophage polarization by activating the notch1 signaling pathway in diabetic nephropathy

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