Vitamin A enhances PI3K/Akt signaling and mitigates enterocyte apoptosis in a mouse model of necrotizing enterocolitis

Pediatr Surg Int. 2025 Jan 8;41(1):61. doi: 10.1007/s00383-025-05963-6.

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.

Keywords: Apoptosis; Necrotizing enterocolitis; Phosphoinositide 3-kinase/Akt signaling pathway; Vitamin A.

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis* / drug effects
  • Blotting, Western
  • Disease Models, Animal*
  • Enterocolitis, Necrotizing* / drug therapy
  • Enterocolitis, Necrotizing* / metabolism
  • Enterocolitis, Necrotizing* / pathology
  • Enterocytes* / drug effects
  • Enterocytes* / metabolism
  • Enterocytes* / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Mice
  • Mice, Inbred C57BL
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction*
  • Vitamin A* / pharmacology

Substances

  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Vitamin A