Vitamin A enhances PI3K/Akt signaling and mitigates enterocyte apoptosis in a mouse model of necrotizing enterocolitis
link.springer.com shows its articles on its own site.
Read the article on link.springer.com ↗Article · Jan 2025 · 1 min read
In brief
In brief
This preclinical study demonstrates that vitamin A supplementation reduces intestinal cell death in a mouse model of necrotizing enterocolitis (NEC) by activating the PI3K/Akt survival pathway and modulating apoptotic proteins. The findings suggest vitamin A may offer therapeutic potential for preventing enterocyte damage in this devastating neonatal intestinal disease.
- NEC pathogenesis involves downregulation of PI3K/Akt survival signaling and upregulation of pro-apoptotic factors (Bax, CytoC, Caspase 3).
- Vitamin A supplementation restores PI3K/Akt pathway activity and reduces enterocyte apoptosis in experimental NEC models.
- Vitamin A shifts the apoptotic balance by increasing anti-apoptotic Bcl-2 while decreasing pro-apoptotic mediators.
- Therapeutic vitamin A may protect intestinal epithelium in NEC through modulation of cell survival signaling pathways.
Written by the GCMD Library team from the article.
Abstract
Purpose
This study aims to elucidate the roles of the PI3K-Akt signaling pathway and enterocyte apoptosis in necrotizing enterocolitis (NEC) pathogenesis and investigate the impact of vitamin A intervention on these factors.
Methods
We employed an NEC mouse model and administered vitamin A treatment. Retinol levels in mouse blood were quantified using ELISA. Intestinal cell apoptosis in NEC mice was assessed via the TUNEL assay. We evaluated mRNA and protein expressions of Bcl-2, Bax, cytochrome C (CytoC), Caspase 3, and PI3K/Akt signaling pathway components using qPCR and western blotting.
Results
In NEC models, PI3K, Akt, and Bcl-2 were downregulated, accompanied by upregulated Bax, CytoC, and Caspase 3 at both mRNA and protein levels. These molecular changes were associated with an increase in enterocyte apoptosis in the NEC models. Vitamin A supplementation increased PI3K, Akt, and Bcl-2 expression while decreasing Bax, CytoC, and Caspase 3 levels in the NEC models, resulting in reduced apoptosis.
Conclusion
Vitamin A has the potential to mitigate enterocyte apoptosis in NEC by upregulating the PI3K/Akt signaling pathway and modulating apoptotic signals, providing new insights into the inhibitory effect of vitamin A on enterocyte apoptosis in NEC.