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Integrating bioinformatics and metabolomics to identify potential biomarkers of hypertensive nephropathy

Kezhen Yang1, Pingna Zhang2, Xiaofeng Ding3

  • 1Department of Rehabilitation Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang, China. 767299632@qq.com.

Scientific Reports
|March 3, 2025
PubMed

Insights

Hypertensive nephropathy (HN) involves unclear pathways. This study identified key genes (APOE, ALB, SERPINA1) and bile acids (CA, DCA, TDCA) linked to early HN progression and elevated blood pressure.

Area of Science:

  • Nephrology
  • Biochemistry
  • Genomics

Background:

  • Hypertensive nephropathy (HN) is a major cause of end-stage renal disease, but its pathogenesis remains unclear.
  • Understanding the biological pathways and biomarkers involved in HN progression is crucial for early diagnosis and treatment.

Purpose of the Study:

  • To identify biological pathways implicated in hypertensive nephropathy (HN) progression.
  • To discover bile acid (BA)-related biomarkers for HN.
  • To elucidate the role of bile acids in the development of HN.

Main Methods:

  • Downloaded and analyzed gene microarray data to identify differentially expressed genes (DEGs) in HN.
  • Performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis on DEGs.
  • Constructed a protein-protein interaction (PPI) network and integrated BA targets to identify hub genes.
  • Established an early hypertensive nephropathy animal model (SHR) and quantified 39 bile acids in renal cortex.

Main Results:

  • Identified 398 DEGs and multiple biological pathways associated with hypertension and nephropathy.
  • Discovered three BA-related hub genes: APOE, ALB, and SERPINA1.
  • Found significant concentration differences in seven bile acids (DCA, CDCA, UDCA, UCA, CA, TDCA, TCDCA) in early HN.
  • Observed a positive correlation between specific bile acids (CA, DCA, TDCA) and blood pressure in the SHR model, indicating diagnostic potential.

Conclusions:

  • The identified hub genes (APOE, ALB, SERPINA1) and elevated bile acids, particularly CA, DCA, and TDCA, are likely involved in the early stages of hypertensive nephropathy (HN).
  • These BA-related biomarkers show significant correlation and specificity with blood pressure, suggesting high diagnostic value for early HN detection.

Keywords:
Bile acidBile acid metabolismBioinformaticHypertensive nephropathyMetabolomics

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