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PTGER3 and MMP-2 play potential roles in diabetic nephropathy via competing endogenous RNA mechanisms

Yue Yu1, Yuan-Yuan Jia2, Meng Wang3

  • 1Department of Endocrinology, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin Province, China.

BMC Nephrology
|January 13, 2021
PubMed
Abstract

Insights

This study identified key microRNAs and genes involved in diabetic nephropathy (DN) in type 2 diabetes mellitus (DM). These findings highlight potential therapeutic targets for DN, aiming to improve diagnostic accuracy and treatment strategies.

Area of Science:

  • Genomics and Molecular Biology
  • Nephrology
  • Endocrinology

Background:

  • Diabetic nephropathy (DN) is a major complication of diabetes mellitus (DM) with unclear pathology and insufficient diagnostic accuracy.
  • Identifying novel therapeutic targets is crucial for managing DN in type 2 DM patients.

Purpose of the Study:

  • To identify microRNAs (miRNAs) and genes as potential therapeutic targets for DN.
  • To explore the competing endogenous RNA (ceRNA) network in DN pathogenesis.

Main Methods:

  • Downloaded human miRNA (GSE51674) and gene (GSE111154) data from the Gene Expression Omnibus database.
  • Screened for differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) in kidney tissues.
  • Constructed a ceRNA network to identify key lncRNA-miRNA-mRNA interactions and screened for potential drugs targeting DEGs.

Main Results:

  • Identified 83 DEmiRNAs and 293 DEGs. Key ceRNA networks involved RP11-363E7.4/TTN-AS1/HOTAIRM1-hsa-miR-106b-5p-PTGER3 and LINC00960-hsa-miR-1237-3p-MMP-2.
  • Found PTGER3 and hsa-miR-1237-3p downregulated, while MMP-2 and hsa-miR-106b-5p were upregulated in DN kidneys.
  • Confirmed deregulation of PTGER3 and MMP-2 in plasma samples from DN patients and identified potential drugs targeting these genes.

Conclusions:

  • The identified ceRNA networks, RP11-363E7.4/TTN-AS1/HOTAIRM1-hsa-miR-106b-5p-PTGER3 and LINC00960-hsa-miR-1237-3p-MMP-2, are potentially associated with diabetic renal injury.
  • PTGER3 and MMP-2 represent promising therapeutic targets for DN, with drugs like iloprost, treprostinil, or captopril showing potential.
Keywords:
Diabetic nephropathyMicroarrayMolecular biologyType 2 diabetes mellitusmicroRNAs

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