LncRNA SNHG7/miR-181b-5p/TLR4 Activates Inflammation And Promotes Pyroptosis Through NF-κB Signaling in Diabetic Nephropathy

Inflammation. 2025 Dec;48(6):3828-3840. doi: 10.1007/s10753-025-02295-4. Epub 2025 May 15.

Abstract

MiR-181b-5p plays a critical role in the pyroptosis and injury of kidney tubular cells in diabetic kidney disease (DKD). The long noncoding RNA (lncRNA) small nucleolar RNA hostgene 7 (SNHG7) has been shown to bind to and inhibit the function of miR-181b-5p. However, the precise role of SNHG7 in DKD remains unclear. To address this, the current study measured the expression levels of SNHG7, miR-181b-5p, and Toll-like receptor 4 (TLR4) using RT-qPCR analysis of renal biopsies from both normal individuals and patients with DKD. An in vitro DKD model was subsequently established by exposing HK-2 cells to high glucose (HG). In both DKD tissues and HG-stimulated HK-2 cells, SNHG7 and TLR4 levels were significantly elevated, while miR-181b-5p levels were markedly reduced. Knockdown of SNHG7 resulted in multiple beneficial effects: it effectively attenuated high glucose-induced lactate dehydrogenase (LDH) leakage, restored cell viability, inhibited the production of inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin 18 (IL-18), and interleukin 1β (IL-1β), and suppressed the activation of the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3)/acysteinyl aspartate-specific proteinase 1 (caspase-1)/gasdermin D (GSDMD) pathway. Mechanistically, SNHG7 functions as a molecular sponge for miR-181b-5p, while miR-181b-5p directly targets TLR4, collectively regulating nuclear factor-kappaB (NF-κB) pathway activation. Moreover, inhibition of miR-181b-5p or up-regulation of TLR4 reversed the protective effects of SNHG7 knockdown. Additionally, co-transfection of a TLR4 over-expression vector with a miR-181b-5p mimic counteracted the effects of miR-181b-5p overexpression on cell viability, LDH leakage, and the expression of inflammatory factors and pyroptosis-related molecules. In summary, SNHG7 acts as a molecular sponge for miR-181b-5p, promoting inflammation and pyroptosis in DKD, which in turn regulates TLR4 expression and the NF-κB signaling pathway.

Keywords: Diabetic kidney disease; Inflammatory response; MiR-181b-5p; Pyroptosis; SNHG7; TLR4.

MeSH terms

  • Base Sequence
  • Biopsy
  • Cell Line
  • Diabetic Nephropathies* / genetics
  • Diabetic Nephropathies* / metabolism
  • Diabetic Nephropathies* / pathology
  • Gene Expression Regulation
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • NF-kappa B / metabolism
  • Pyroptosis*
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Signal Transduction*
  • Toll-Like Receptor 4* / genetics
  • Toll-Like Receptor 4* / metabolism

Substances

  • RNA, Long Noncoding
  • MIrn181 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • TLR4 protein, human
  • Toll-Like Receptor 4