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Identification of potential anti aging drugs and targets in chronic kidney disease
Qian Zhang1, Bing Bai2, Lidan Ran3
1Integrative Medicine & Healthy Center, The First People's Hospital of Zunyi, The Third Affiliated Hospital of Zunyi Medical University, 98 Fenghuang Road, Zunyi, 563002, Guizhou, China. zw19891003@qq.com.
Insights
This study identifies aging-associated genes and potential anti-aging drugs, like Cinnamaldehyde, to treat chronic kidney disease (CKD). Findings suggest targeting these aging pathways could delay CKD progression and offer new therapeutic strategies.
Area of Science:
- Biomedical research
- Bioinformatics
- Genomics
Background:
- Chronic kidney disease (CKD) is a prevalent, untreatable condition often linked to aging.
- Effective therapeutic strategies for CKD remain limited.
- Aging processes significantly influence kidney disease development and progression.
Purpose of the Study:
- To identify potential anti-aging drugs and therapeutic targets for CKD using bioinformatics.
- To explore the molecular mechanisms linking aging and CKD.
- To discover novel therapeutic avenues for managing CKD.
Main Methods:
- Analysis of GEO datasets (GSE37171, GSE66494) to identify differentially expressed genes (DEGs).
- Integration of DEGs with aging-related genes to pinpoint aging-associated differential genes (ARDEGs).
- Construction of protein-protein interaction (PPI) networks and identification of hub genes using STRING and Cytoscape; drug screening via ceRNA, transcription factor networks, and DGldb database.
Main Results:
- Identified 317 DEGs and 23 ARDEGs, with SOD2, FGF21, FOS, RELA, DDIT4, BMI1, DUSP6, LGALS3, CXCR2, and CEBPB highlighted as key regulatory genes in CKD.
- Discovered Cinnamaldehyde as a potential anti-aging drug targeting aging-associated pathways relevant to CKD.
- Validated reduced expression of Cinnamaldehyde targets DDIT4 and DUSP6 in a unilateral ureteral obstruction (UUO) animal model and demonstrated Cinnamaldehyde's efficacy in reducing fibrosis markers in vitro.
Conclusions:
- This research elucidates aging-related molecular targets in CKD, offering a foundation for developing anti-aging therapies.
- Cinnamaldehyde shows promise as a therapeutic agent for delaying CKD progression by modulating aging-associated pathways.
- The study opens new avenues for treating CKD by focusing on its aging components.
Abstract:
Chronic kidney disease (CKD) is highly prevalent, incurable, and lacks effective treatments. Aging is closely linked to various kidney diseases. In this study, we combined CKD and aging using bioinformatics approaches to identify potential anti aging drugs and therapeutic targets for CKD. We analyzed datasets GSE37171 and GSE66494 from the GEO database, identifying 317 differentially expressed genes (DEGs). By intersecting these DEGs with aging related genes, we identified 23 aging associated differential genes (ARDEGs). A protein-protein interaction (PPI) network was constructed using the STRING database, and the top 10 hub ARDEGs were identified using Cytoscape software. Potential anti aging drugs, including Cinnamaldehyde, were identified through the ceRNA and transcription factor regulatory networks, as well as the DGldb database. Among the key regulatory genes identified in CKD patient samples were SOD2, FGF21, FOS, RELA, DDIT4, BMI1, DUSP6, LGALS3, CXCR2, and CEBPB. Cinnamaldehyde and other drugs were found to target aging associated pathways, suggesting their potential to delay CKD progression through modulating these pathways. Finally, we verified the low-expression of DDIT4 and DUSP6, the two targets of Cinnamaldehyde, in unilateral ureteral obstruction (UUO) animal model. Additionally, Cinnamaldehyde was shown to reduce the expression of fibrosis markers such as fibronectin (FN) and α-smooth muscle actin (α-SMA) in HK2 cells under TGF-β1 stimulation. This study provides a foundational understanding of aging related molecular targets in CKD and offers new directions for developing anti aging therapies to treat CKD.
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