Molecular mechanism of programmed cell death in the gut epithelium of neonatal piglets

Michał M. Godlewski*, N. Hallay, J. B. Bierła, R. Zabielski

*Corresponding author for this work

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

In the intestinal mucosa of pig, calf and rat neonates, we observed the cells die in the packets which suggests involvement of some paracrine factors. The death signal was transferred via tissue continuum as well as across the gut lumen, and the involvement of TGF-β1 and TNFα was demonstrated. Present study aimed to clarify the molecular mechanisms of programmed cell death in the mucosa of the small intestine of pig neonates. Groups (packets) of cells and the neighboring cells underwent apoptosis, and expressed an enhanced TGF-RII. In the dying cells the death signal promoted via TGF-RII was associated with enhanced expression of active caspase 8, TGF-β1, TNFα and Bid. Quantitative study showed that high expression of TGF-β1 was positively correlated with expression of BID and negatively with BCL-2, illustrating the transmission of signal from TGF-RII through SMAD cascade and RunX protein. We hypothesize that TGF-β1 sensitizes the enterocytes for TNFα signaling and both cytokines control the apoptosis process in the gut epithelium. Intensive mitosis triggers many errors in DNA replication, and the role of p53 is to detect them and promote either repair or apoptosis. During first days of live all damaged cells were directed towards apoptosis while at day 7 at least some of them were repaired. Autophagy, the second form of programmed cell death, was recognized by its key marker MAP I LC3. Our data showed the colocalization of MAP I LC3 with active caspase 3 thus suggesting a coexistence between these two forms of cell death, at least in the early postnatal life.

Original languageEnglish
Pages (from-to)97-113
Number of pages17
JournalJournal of Physiology and Pharmacology
Volume58
Issue numberSUPPL. 3
Publication statusPublished - Aug 2007

Keywords

  • Apoptosis
  • Autophagy
  • DNA damage
  • Enterocyte turnover
  • TGF-β1
  • TNFα

Fingerprint Dive into the research topics of 'Molecular mechanism of programmed cell death in the gut epithelium of neonatal piglets'. Together they form a unique fingerprint.

  • Cite this

    Godlewski, M. M., Hallay, N., Bierła, J. B., & Zabielski, R. (2007). Molecular mechanism of programmed cell death in the gut epithelium of neonatal piglets. Journal of Physiology and Pharmacology, 58(SUPPL. 3), 97-113.