Integrative transcriptome analysis reveals Serpine2 promotes glomerular mesangial cell proliferation and extracellular matrix accumulation via activating ERK1/2 signalling pathway in diabetic nephropathy DOI
Ting Zheng,

Ruhao Yang,

Xin Li

et al.

Diabetes Obesity and Metabolism, Journal Year: 2024, Volume and Issue: 27(2), P. 750 - 766

Published: Nov. 18, 2024

Abstract Background Diabetic nephropathy (DN) is one of the main causes end‐stage renal disease (ESRD), but its mechanism has not been clearly studied. We utilized integrative transcriptome analysis to explore pathogenesis DN. Methods conducted an by combining bulk dataset and single‐cell dataset. Through this approach, we identified that Serpine2 may regulate ‘collagen‐containing extracellular matrix’ pathway involved in Subsequently, established DN animal cell models using db/db mice mesangial cells (MCs) validate role In model, detected expression level western blotting (WB) immunofluorescence (IF) assays. To further clarify molecular DN, knocked down observed effects on MCs proliferation matrix (ECM) accumulation. Results Our highlighted a pivotal for disease's initiation. Next, through Cytoscape differentially expressed genes (DEGs) MCs, following 10 hub genes: Acta2, Angpt2, Ccn1, Col4a1, Col4a2, Col8a1, Kdr, Thbs1, Tpm4 Serpine2. Kdr were also significantly DEGs glomeruli. Additionally, our integrated gene set enrichment RNA revealed was key progression. crucial regulating pathway. Therefore, speculated regulation important mechanism. Importantly, WB IF staining confirmed upregulated diabetic mice. Knockdown cultured alleviated high‐glucose‐induced excessive ECM Finally, found ERK agonist Ro 67‐7476 eliminated effect siRNA. Conclusions summary, regulates synthesis activation ERK1/2 pathway, which These findings offer fresh perspectives mechanisms glomerulosclerosis provide new targets treating

Language: Английский

New insights into the mechanism of triphenyl phosphate and its metabolite diphenyl phosphate in diabetic kidney disease DOI Creative Commons
Ting Fang, Qiaoyan Liu,

Xinxin Huangfu

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 291, P. 117877 - 117877

Published: Feb. 1, 2025

Diabetic kidney disease is a significant complication of diabetes mellitus, and exposure to certain chemicals may play role in its development. Triphenyl phosphate (TPHP) commonly used plastics flame retardants. This study aims investigate the potential impact TPHP metabolite diphenyl (DPHP) on diabetic using various methods, including network toxicology, molecular docking, cell experiments like CCK8 assay real-time-PCR. The research examined relationship between urinary DPHP levels function American adults data from National Health Nutrition Examination Survey (NHANES) 2017 March 2020. Additionally, explored targets action for toxicity analysis, conducted protein interaction functional aspects through Gene Ontology Kyoto Encyclopedia Genes Genomes enrichment analysis. Furthermore, identified key proteins involved experimental verification by treating cells with DPHP. Toxicity analysis showed that could cause dose-dependent mouse podocyte clone 5 (MPC5) mesangial (MES13). also detected mRNA expression core molecularly docked results indicated statistically regulation most MPC5, MES13, human kidney-2 cells.

Language: Английский

Citations

0
Natural products combating EGFR-TKIs resistance in cancer DOI Creative Commons
Xia Li,

Gaohui Zhu,

Qiyao Peng

et al.

European Journal of Medicinal Chemistry Reports, Journal Year: 2025, Volume and Issue: unknown, P. 100251 - 100251

Published: Feb. 1, 2025

Language: Английский

Citations

0
Vaccarin Ameliorates Renal Fibrosis by Inhibiting Ferroptosis via Nrf2/SLC7A11/GPX4 Signaling Pathway DOI Creative Commons

Mengjiao Cui,

Qiming Xu,

Lianxiang Duan

et al.

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 1609 - 1626

Published: March 1, 2025

Purpose: Vaccarin is a natural flavonoid glycoside with anti-inflammatory, antioxidant and nephroprotective effects. However, the effects of vaccarin on renal fibrosis (RF) its molecular mechanisms remain unclear. This study aimed to investigate RF mechanisms. Methods: Network pharmacology was used analyze effect RF, docking dynamics simulations were performed assess binding nuclear factor erythroid 2-related 2 (Nrf2) vaccarin. A mouse model unilateral ureteral obstruction (UUO) established in vivo, human tubular epithelial (HK2) cells induced transforming growth factor-β (TGF-β) RSL3, respectively, as an vitro model. The anti-fibrotic observed by histopathological staining determination fibrous markers. Changes oxidative stress ferroptosis-related markers detected kits, Western blot (WB), qRT-PCR immunofluorescence (IF). Finally, Nrf2 inhibitors added observe ferroptosis. Results: cross genes are enriched for stress. binds stably Both vivo experiments showed that treatment reduced expression markers, decreased levels reactive oxygen species (ROS), malondialdehyde (MDA), lipid peroxidation (LPO) Fe 2+ , increased glutathione (GSH) secretion. In addition, down-regulated Long-chain acyl-CoA synthetase 4 (ACSL4), prostaglandin-endoperoxide synthase (PTGS2) NADPH oxidase 1 (NOX1), up-regulated downstream solute transport family 7 member 11 (SLC7A11) peroxidase (GPX4) expression. Mechanistic studies indicated activated Nrf2/SLC7A11/GPX4 pathway inhibit ferroptosis, this inhibition effectively reversed inhibitor. Conclusion: ameliorates inhibiting ferroptosis via pathway. Keywords: vaccarin, fibrosis, pathway, stress, network

Language: Английский

Citations

0
Integrative transcriptome analysis reveals Serpine2 promotes glomerular mesangial cell proliferation and extracellular matrix accumulation via activating ERK1/2 signalling pathway in diabetic nephropathy DOI
Ting Zheng,

Ruhao Yang,

Xin Li

et al.

Diabetes Obesity and Metabolism, Journal Year: 2024, Volume and Issue: 27(2), P. 750 - 766

Published: Nov. 18, 2024

Abstract Background Diabetic nephropathy (DN) is one of the main causes end‐stage renal disease (ESRD), but its mechanism has not been clearly studied. We utilized integrative transcriptome analysis to explore pathogenesis DN. Methods conducted an by combining bulk dataset and single‐cell dataset. Through this approach, we identified that Serpine2 may regulate ‘collagen‐containing extracellular matrix’ pathway involved in Subsequently, established DN animal cell models using db/db mice mesangial cells (MCs) validate role In model, detected expression level western blotting (WB) immunofluorescence (IF) assays. To further clarify molecular DN, knocked down observed effects on MCs proliferation matrix (ECM) accumulation. Results Our highlighted a pivotal for disease's initiation. Next, through Cytoscape differentially expressed genes (DEGs) MCs, following 10 hub genes: Acta2, Angpt2, Ccn1, Col4a1, Col4a2, Col8a1, Kdr, Thbs1, Tpm4 Serpine2. Kdr were also significantly DEGs glomeruli. Additionally, our integrated gene set enrichment RNA revealed was key progression. crucial regulating pathway. Therefore, speculated regulation important mechanism. Importantly, WB IF staining confirmed upregulated diabetic mice. Knockdown cultured alleviated high‐glucose‐induced excessive ECM Finally, found ERK agonist Ro 67‐7476 eliminated effect siRNA. Conclusions summary, regulates synthesis activation ERK1/2 pathway, which These findings offer fresh perspectives mechanisms glomerulosclerosis provide new targets treating

Language: Английский

Citations

0