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image of Reversal of Mucin 1 Reduction-Induced Enterocyte Apoptosis by Retinoic Acid through the PI3K/AKT Signaling Pathway in an In vitro Model of Necrotizing Enterocolitis

Abstract

Objective

This study aimed to investigate the roles of Mucin 1 (MUC1), the PI3K/AKT pathway, and enterocyte apoptosis in Necrotizing Enterocolitis (NEC).

Methods

Using an NEC Caco-2 cell model, retinoic acid treatment and MUC1 gene silencing were employed. Flow cytometry was used to assess apoptosis, while quantitative PCR and western blot analyses were conducted to evaluate the gene and protein expressions of MUC1, PI3K, Akt, and factors related to apoptotic modulation.

Results

In comparison to the control group, NEC induction resulted in a significant reduction in MUC1 expression, accompanied by an elevation in enterocyte apoptosis. In NEC and Si-MUC1 Caco-2 cells, downregulation of PI3K/AKT signals and Bcl-2 was observed, while upregulation of Bax, CytoC, and Caspase 3 at both mRNA and protein levels was prominent. Retinoic acid supplementation exhibited a noteworthy increase in MUC1, AKT, and Bcl-2 mRNA and protein expressions, coupled with a decrease in Bax, CytoC, and Caspase 3, thereby mitigating apoptosis in NEC.

Conclusion

Our findings suggested that reduced MUC1 expression in NEC contributes to the upregulation of enterocyte mitochondrial apoptosis through the PI3K/AKT signaling pathway. Retinoic acid supplementation emerges as a potential therapeutic strategy for NEC, demonstrating its ability to upregulate MUC1 expression and attenuate apoptosis via the PI3K/AKT signaling pathway.

© 2025 Bentham Science Publishers
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/content/journals/cmm/10.2174/0115665240337176241204070150
2025-01-15
2025-03-18

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/content/journals/cmm/10.2174/0115665240337176241204070150
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Reversal of Mucin 1 Reduction-Induced Enterocyte Apoptosis by Retinoic Acid through the PI3K/AKT Signaling Pathway in an In vitro Model of Necrotizing Enterocolitis
Bentham Science Publishers ; https://doi.org/10.2174/0115665240337176241204070150
/content/journals/cmm/10.2174/0115665240337176241204070150
/content/journals/cmm/10.2174/0115665240337176241204070150
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  • Article Type:     Research Article
Keywords: Necrotizing enterocolitis ; MUC1 ; phosphoinositide 3-kinase/Akt signaling pathway ; apoptosis ; Caco-2 cell ; retinoic acid

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