Downregulation of hsa-miR-100-5p May Be a Protective Factor in the Early Stages of Nephropathy in Type 1 Diabetes Mellitus

Int J Mol Sci. 2024 May 23;25(11):5663. doi: 10.3390/ijms25115663.

Abstract

Type 1 Diabetes Mellitus (T1DM) can generate severe complications, such as Diabetic Kidney Disease (DKD) or Diabetic Nephropathy (DN), with it emerging as the leading cause of terminal (end-stage) renal disease all over the world. For T1DM, the clinical evaluation of DKD uses markers like the Glomerular Filtration Rate (GFR) and the Urinary Albumin Excretion (UAE). However, early diagnosis of DKD is still a challenge. For this reason, investigating molecular markers, such as microRNAs (miRNAs), offers a promising perspective to an early diagnosis, highlighting the stability and the ability to reflect incipient molecular manifestations. Thus, here we investigated four miRNAs (hsa-let-7i-5p, hsa-miR-143-3p, hsa-miR-501-3p, and hsa-miR-100-5p) regarding nephropathy in patients with T1DM, considering the albuminuria (micro and macro) as a standard to evaluate the groups. As a result, we found a reduced expression of miR-100-5p in patients with MIC, indicating a protective role in nephropathy. Beyond that, expression levels between the groups (Non vs. UAE) were not significant when comparing the miRNAs miR-501-3p and miR-143-3p. Finally, miR-143-3p and miR-100-5p were linked to some target genes such as AKT1, MMP13, and IGF1R, that are connected to signal pathways and cellular metabolism.

Keywords: diabetic kidney disease; diabetic nephropathy; hsa-miR-100-5p; miRNAs; type 1 diabetes mellitus.

MeSH terms

  • Adult
  • Albuminuria / genetics
  • Biomarkers* / analysis
  • Diabetes Mellitus, Type 1* / complications
  • Diabetes Mellitus, Type 1* / genetics
  • Diabetic Nephropathies* / genetics
  • Diabetic Nephropathies* / metabolism
  • Down-Regulation / genetics
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Male
  • MicroRNAs* / genetics
  • Middle Aged
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism

Substances

  • Biomarkers
  • IGF1R protein, human
  • MicroRNAs
  • MIRN100 microRNA, human
  • Receptor, IGF Type 1