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Identification of potential therapeutic target genes in mouse mesangial cells associated with diabetic nephropathy

Xin Mou1, Di Yi Zhou1, Ying Hui Liu1

  • 1Department of Endocrinology, Zhejiang Integrated and Western Medicine Hospital, Hangzhou, Zhejiang 310003, P.R. China.

Experimental and Therapeutic Medicine
|May 21, 2019
PubMed

Insights

This study identified key genes like Jun and RHOB involved in diabetic nephropathy (DN) by analyzing gene expression changes in mesangial cells. These genes may offer new therapeutic targets for treating DN.

Area of Science:

  • Molecular Biology
  • Genomics
  • Nephrology

Background:

  • Diabetic nephropathy (DN) is a major complication of diabetes, characterized by progressive kidney damage.
  • Understanding the molecular mechanisms underlying DN is crucial for developing effective treatments.

Purpose of the Study:

  • To identify genes affected by transforming growth factor-β (TGF-β1), high glucose (HG), and glucosamine (GlcN) in MES-13 mesangial cells.
  • To elucidate the molecular mechanisms of diabetic nephropathy (DN).

Main Methods:

  • Downloaded and analyzed gene expression datasets (GSE2557, GSE2558) from the Gene Expression Omnibus database.
  • Screened differentially expressed genes (DEGs) using GEO2R and performed Gene Ontology and KEGG pathway enrichment analyses.
  • Constructed protein-protein interaction (PPI) networks and identified hub and overlapping genes for molecular docking analysis.

Main Results:

  • Identified numerous DEGs in response to TGF-β1, HG, and GlcN treatments.
  • Enriched pathways included 'nucleosome assembly', 'chromatin silencing', 'xenobiotic glucuronidation', 'systemic lupus erythematosus', 'protein processing in endoplasmic reticulum', 'aldarate metabolism', and 'TNF signaling pathway'.
  • Selected eight hub genes (Jun, Ptgs2, Fn1, Cdk2, Fos, Hspa5, Hsp90b1, Hyou1) and three overlapping genes (RHOB, CFH, KLF15) with potential therapeutic relevance.

Conclusions:

  • Jun, Ptgs2, Fn1, Cdk2, Fos, Hspa5, Hsp90b1, Hyou1, RHOB, CFH, and KLF15 are potential therapeutic targets for mesangial cells in DN.
  • These findings may offer novel insights into DN treatment strategies.
  • Molecular docking revealed potential drug interactions, such as Valsartan with RHOB and Fosinopril with CFH and KLF15.
Keywords:
bioinformaticsdiabetic nephropathiesdifferentially expressed genesmesangial cells

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