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

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY Tissue & cell Pub Date : 2025-01-07 DOI:10.1016/j.tice.2025.102724

Sherein F. El-sayed , Samar Mortada Mahmoud , Walaa Samy , Reham M. Wahid , Aliaa Talaat , Sara G. Seada

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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.

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维生素D3通过调节胃因子、E-cadherin、抑制NLRP3和NF-κB/MMP-9信号通路减轻阿司匹林诱导的胃损伤。

背景：胃溃疡的患病率在现代显著增长，影响全球人口的10% %。阿司匹林下调胃黏膜胃因子1（GKN1）表达，导致胃癌发生。维生素D3（维生素D3）具有抗炎和抗氧化作用。目的：研究维生素d对胃的保护作用。D3在阿司匹林诱导胃损伤后与胃因子的关系，并探讨可能的潜在机制。材料与方法：将24只大鼠分为4组：对照组、Vit组。D3补充正常，阿司匹林诱导的胃损伤，和Vit。D3补充胃损伤组。测定胃组织中gkn1和2、粘蛋白5AC （Muc5ac）和NLR家族pyrin domain containing 3 （NLRP3）基因表达的氧化应激标志物。对胃黏膜E-Cadherin、核因子κ b （NFκB）、金属蛋白酶9 （MMP-9）进行组织病理学和免疫组化检测。结果:服用维生素。补充D3可显著上调胃组织中的E-Cadherin、GSH、GKN1和Muc5ac。通过减轻氧化应激、nf - κ b、MMP-9和炎性小体（NLRP3）的下调，改善胃组织的形态学和组织学。结论：维生素D3通过上调胃动素1和E-cadherin，下调NFKB/MMP-9信号通路和NLRP3炎性体，对阿司匹林诱导的胃损伤具有潜在的保护作用。

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.