Vitamin D3 mitigates aspirin-induced gastric injury by modulating gastrokines, E-cadherin, and inhibiting NLRP3 and NF-κB/MMP-9 signaling pathway

Tissue Cell. 2025 Apr:93:102724. doi: 10.1016/j.tice.2025.102724. Epub 2025 Jan 7.

Abstract

Background: The prevalence of gastric ulcers has grown significantly in the modern era affecting 10 % of global population. Aspirin downregulates gastrokines 1(GKN1) expression in gastric mucosa and GKN1 down-regulation results in gastric cancer. Vitamin D3 (Vit.D3) has anti-inflammatory and antioxidant effects.

Aim: Study the gastroprotective impact of Vit.D3 following aspirin-induced gastric injury in relation to gastrokines and investigate the possible underlying mechanisms.

Materials and methods: 24 rats were divided into 4 groups: control, Vit.D3 supplemented normal, aspirin-induced gastric injury, and Vit.D3 supplemented gastric injury groups. Some oxidative stress markers with gene expression of GKN1&2, mucin 5AC (Muc5ac) and NLR family pyrin domain containing 3 (NLRP3) in the gastric tissue were done. Histopathological and immunohistochemical study of E-Cadherin, nuclear factor kappa beta (NFκB), and metalloproteinase-9 (MMP-9) in the stomach mucosa were identified.

Results: Vit.D3 supplementation significantly upregulated E-Cadherin, GSH, GKN1 and Muc5ac in the gastric tissue. Also, it improved the morphology, histology of gastric tissue, by alleviating oxidative stress and NFκB, MMP-9 and down regulation of inflammasome (NLRP3).

Conclusion: Vitamin D3 has a potential protective effect against aspirin -induced gastric injury via upregulating gastrokine1 and E-cadherin and down regulation of NFKB/MMP-9 signaling pathway and NLRP3 inflammasome.

Keywords: Aspirin; Gastric injury; Gastrokines; Vitamin D.

MeSH terms

  • Animals
  • Aspirin* / adverse effects
  • Cadherins* / metabolism
  • Cholecalciferol* / pharmacology
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Male
  • Matrix Metalloproteinase 9* / metabolism
  • NF-kappa B* / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Oxidative Stress / drug effects
  • Rats
  • Signal Transduction* / drug effects
  • Stomach Ulcer* / chemically induced
  • Stomach Ulcer* / drug therapy
  • Stomach Ulcer* / pathology

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NF-kappa B
  • Aspirin
  • Cholecalciferol
  • Matrix Metalloproteinase 9
  • Cadherins
  • Nlrp3 protein, rat
  • Mmp9 protein, rat