Skip to content
2000
Volume 25, Issue 11
  • ISSN: 1566-5240
  • E-ISSN: 1875-5666

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
Loading

Article metrics loading...

/content/journals/cmm/10.2174/0115665240337176241204070150
2025-01-15
2026-01-01

  • From This Site

    /content/journals/cmm/10.2174/0115665240337176241204070150
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. DuessJ.W. SampahM.E. LopezC.M. Necrotizing enterocolitis, gut microbes, and sepsis.Gut Microbes2023151222147010.1080/19490976.2023.2221470 37312412
     [Google Scholar]
  2. NeuJ. Necrotizing enterocolitis: The future.Neonatology2020117224024410.1159/000506866 32155645
     [Google Scholar]
  3. LiuD. XuY. FengJ. YuJ. HuangJ. LiZ. Mucins and tight junctions are severely altered in necrotizing enterocolitis neonates.Am. J. Perinatol.202138111174118010.1055/s‑0040‑1710558 32446259
     [Google Scholar]
  4. LiW. HanY. SunC. Novel insights into the roles and therapeutic implications of MUC1 oncoprotein via regulating proteins and non-coding RNAs in cancer.Theranostics2022123999101110.7150/thno.63654 35154471
     [Google Scholar]
  5. DharP. McAuleyJ. The role of the cell surface mucin MUC1 as a barrier to infection and regulator of inflammation.Front. Cell. Infect. Microbiol.2019911710.3389/fcimb.2019.00117 31069176
     [Google Scholar]
  6. RajabiH. HirakiM. KufeD. MUC1-C activates polycomb repressive complexes and downregulates tumor suppressor genes in human cancer cells.Oncogene201837162079208810.1038/s41388‑017‑0096‑9 29379165
     [Google Scholar]
  7. MurthyD. AttriK.S. SinghP.K. Phosphoinositide 3-kinase signaling pathway in pancreatic ductal adenocarcinoma progression, pathogenesis, and therapeutics.Front. Physiol.2018933510.3389/fphys.2018.00335 29670543
     [Google Scholar]
  8. GaoJ. CaoB. ZhaoR. LiH. XuQ. WeiB. Critical signaling transduction pathways and intestinal barrier: Implications for pathophysiology and therapeutics.Pharmaceuticals2023169121610.3390/ph16091216 37765024
     [Google Scholar]
  9. XiaoS. LiQ. HuK. Vitamin A and retinoic acid exhibit protective effects on necrotizing enterocolitis by regulating intestinal flora and enhancing the intestinal epithelial barrier.Arch. Med. Res.20184911910.1016/j.arcmed.2018.04.003 29699808
     [Google Scholar]
  10. YangS. WeiX. ZhongY. Programmed death of intestinal epithelial cells in neonatal necrotizing enterocolitis: A mini-review.Front Pediatr.202311119987810.3389/fped.2023.1199878 37342533
     [Google Scholar]
  11. YangJ. ShiY. Paneth cell development in the neonatal gut: Pathway regulation, development, and relevance to necrotizing enterocolitis.Front. Cell Dev. Biol.202311118415910.3389/fcell.2023.1184159 37266449
     [Google Scholar]
  12. SupruniukK. RadziejewskaI. MUC1 is an oncoprotein with a significant role in apoptosis. (Review)Int. J. Oncol.20215936810.3892/ijo.2021.5248 34278474
     [Google Scholar]
  13. McAuleyJ.L. LindenS.K. PngC.W. MUC1 cell surface mucin is a critical element of the mucosal barrier to infection.J. Clin. Invest.200711782313232410.1172/JCI26705 17641781
     [Google Scholar]
  14. BallesterB. MilaraJ. CortijoJ. The role of mucin 1 in respiratory diseases.Eur. Respir. Rev.20213015920014910.1183/16000617.0149‑2020 33536260
     [Google Scholar]
  15. HeY. DuW. XiaoS. Colonization of fecal microbiota from patients with neonatal necrotizing enterocolitis exacerbates intestinal injury in germfree mice subjected to necrotizing enterocolitis-induction protocol via alterations in butyrate and regulatory T cells.J. Transl. Med.202119151010.1186/s12967‑021‑03109‑5 34922582
     [Google Scholar]
  16. AnL. LiJ. LiuB. Knockdown of TRPM7 attenuates apoptosis and inflammation in neonatal necrotizing enterocolitis model cell IEC-6 via modulating TLR4/NF-κB and MEK/ERK pathways.Iran. J. Basic Med. Sci.202225894795310.22038/ijbms.2022.62113.13742 36159330
     [Google Scholar]
  17. GomartA. ValléeA. LecarpentierY. Necrotizing enterocolitis: LPS/TLR4-induced crosstalk between canonical TGF-β/Wnt/β-catenin pathways and PPARγ.Front Pediatr.2021971334410.3389/fped.2021.713344 34712628
     [Google Scholar]
  18. AtesU. GolluG. KucukG. Increase in pro-apoptotic bax expression and decrease in anti-apoptotic Bcl-2 expression in newborns with necrotizing enterocolitis.Arch. Argent. Pediatr.2016114324324710.5546/aap.2016.eng.243 27164337
     [Google Scholar]
  19. LiuB. PanS. XiaoY. LiuQ. XuJ. JiaL. LINC01296/miR-26a/GALNT3 axis contributes to colorectal cancer progression by regulating O-glycosylated MUC1 via PI3K/AKT pathway.J. Exp. Clin. Cancer Res.201837131610.1186/s13046‑018‑0994‑x 30547804
     [Google Scholar]
  20. ImdadA. RehmanF. DavisE. Effect of synthetic vitamin A and probiotics supplementation for prevention of morbidity and mortality during the neonatal period. a systematic review and meta-analysis of studies from low- and middle-income countries.Nutrients202012379110.3390/nu12030791 32192165
     [Google Scholar]
  21. KimS.W. SeoK.Y. RhimT. KimE.K. Effect of retinoic acid on epithelial differentiation and mucin expression in primary human corneal limbal epithelial cells.Curr. Eye Res.2012371334210.3109/02713683.2011.620728 22029601
     [Google Scholar]
  22. XuG. MaT. ZhouC. ZhaoF. PengK. LiB. β-carotene attenuates apoptosis and autophagy via PI3K/AKT/mTOR signaling pathway in necrotizing enterocolitis model cells IEC-6.Evid. Based Complement. Alternat. Med.2022202211110.1155/2022/2502263 35754683
     [Google Scholar]
  23. HackamD.J. SodhiC.P. Bench to bedside — new insights into the pathogenesis of necrotizing enterocolitis.Nat. Rev. Gastroenterol. Hepatol.202219746847910.1038/s41575‑022‑00594‑x 35347256
     [Google Scholar]
  24. LiuL. ZhouL. WangL. MUC1 attenuates neutrophilic airway inflammation in asthma by reducing NLRP3 inflammasome-mediated pyroptosis through the inhibition of the TLR4/MyD88/NF-κB pathway.Respir. Res.202324125510.1186/s12931‑023‑02550‑y 37880668
     [Google Scholar]
/content/journals/cmm/10.2174/0115665240337176241204070150
Loading
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
Current Molecular Medicine 25, 1405 (2025); https://doi.org/10.2174/0115665240337176241204070150
/content/journals/cmm/10.2174/0115665240337176241204070150
/content/journals/cmm/10.2174/0115665240337176241204070150
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): apoptosis; Caco-2 cell; MUC1; Necrotizing enterocolitis; phosphoinositide 3-kinase/Akt signaling pathway; retinoic acid

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test