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

Sherein F El-Sayed; Samar Mortada Mahmoud; Walaa Samy; Reham M Wahid; Aliaa Talaat; Sara G Seada

doi:10.1016/j.tice.2025.102724

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 Jan 7:93:102724. doi: 10.1016/j.tice.2025.102724. Online ahead of print.

Authors

Sherein F El-Sayed¹, Samar Mortada Mahmoud², Walaa Samy³, Reham M Wahid⁴, Aliaa Talaat⁵, Sara G Seada⁶

Affiliations

¹ Department of Medical Physiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt. Electronic address: [email protected].
² Department of Human Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig, Egypt. Electronic address: [email protected].
³ Department of Medical Biochemistry, Faculty of Medicine, Zagazig University, Zagazig, Egypt. Electronic address: [email protected].
⁴ Department of Medical Physiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt. Electronic address: [email protected].
⁵ Department of Medical Biochemistry, Faculty of Medicine, Zagazig University, Zagazig, Egypt. Electronic address: [email protected].
⁶ Department of Medical Physiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

PMID: 39823708
DOI: 10.1016/j.tice.2025.102724

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.