Revealing the regulatory role of lncRNAs SNHG1 and CRNDE on Th17/Treg imbalance in diabetic kidney disease

Clin Exp Med. 2025 Aug 2;25(1):271. doi: 10.1007/s10238-025-01802-z.

Abstract

Diabetic kidney disease (DKD) is a chronic inflammatory condition associated with diabetes that can progress to end-stage renal disease (ESRD). However, our knowledge about the epigenetic regulatory mechanism underlying the imbalance of Th17/Treg cells in inflammatory responses remains unclear. Therefore, our aim in this study was to identify regulatory lncRNAs involved in differentiating Th17/Treg cell lines. Regulatory lncRNAs associated with DKD were identified by analyzing the GSE43005 and GSE142025 datasets from the GEO database and conducting a comprehensive literature review. After identifying differentially expressed genes (DEGs), we validated our bioinformatics results using real-time PCR. In our study, ninety individuals were recruited and assigned to four groups: 30 with Type 2 Diabetes (T2D), 15 with early-stage DKD (microalbuminuria), 15 with advanced DKD (ESRD), and 30 healthy controls. The correlation between target genes and clinical laboratory findings, such as BUN, creatinine, ESR, GFR, urea, FBS, HbA1C, and 2hpp was assessed. The results indicated that CRNDE, which positively affects the expression of RORC and IL-17 genes, was upregulated in individuals with ESRD and T2D. Conversely, in the Treg cell line, SNHG1, a positive regulator of FOXP3, was significantly downregulated in ESRD, microalbuminuria, and T2D patients. Interestingly, TGF-β cytokine expression was increased in ESRD and microalbuminuria patients. Our findings suggest that SNHG1 and CRNDE may contribute to the regulation of Th17/Treg imbalance and the progression of inflammatory responses in DKD. These genes may serve as novel biomarkers for the diagnosis and prognosis of DKD. Further research into the effects of anti-inflammatory drugs on modulating immune system responses is a critical step toward mitigating kidney damage.

Keywords: Bioinformatics; Diabetic kidney disease; Real-time PCR; Th17; Treg; lncRNA.

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetic Nephropathies* / genetics
  • Diabetic Nephropathies* / immunology
  • Diabetic Nephropathies* / pathology
  • Female
  • Gene Expression Regulation
  • Humans
  • Male
  • Middle Aged
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • T-Lymphocytes, Regulatory* / immunology
  • T-Lymphocytes, Regulatory* / metabolism
  • Th17 Cells* / immunology
  • Th17 Cells* / metabolism

Substances

  • RNA, Long Noncoding
  • CRNDE RNA, human
  • RORC protein, human
  • Nuclear Receptor Subfamily 1, Group F, Member 3