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Experimental ulceration leads to sequential expression of spasmolytic polypeptide, intestinal trefoil factor,
M R Alison1, R Chinery, R Poulsom
1Department of Histopathology, Royal Postgraduate Medical School, London, U.K.
Abstract:
A model of gastric ulceration in the rat has been used to determine the expression of four messenger RNAs (mRNAs) encoding peptides considered to play active parts in the healing response. The trefoil peptides, rat spasmolytic polypeptide (rSP) and rat intestinal trefoil factor (rITF), along with epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) were the molecules studied. Ulceration was caused under anaesthesia by brief application of a liquid nitrogen-filled cryoprobe to the gastric serosal surface and RNA expression was monitored over the next 10 days. Each mRNA was quantified by ribonuclease protection assay, and mRNAs encoding rSP and rITF were localized within tissue sections by hybridization in situ with 35S antisense riboprobes. Ulceration induced the very rapid expression of first rSP and then rITF mRNA, whereas the mRNAs encoding EGF and TGF alpha increased at later times, with maxima recorded at 3 and 6 days, respectively. Hybridization in situ detected extensive rSP mRNA expression in the regenerative epithelia. The pronounced, but temporally different patterns of mRNA induction after ulceration suggest that the trefoil peptides may fulfil different and more immediate roles than the more 'traditional' healing proteins EGF and TGF alpha.
Insights
Gastric ulceration rapidly upregulates trefoil peptide mRNAs (rSP, rITF), suggesting immediate roles in healing. Epidermal growth factor (EGF) and transforming growth factor alpha (TGFα) mRNA expression occurs later.
Area of Science:
- Gastroenterology
- Molecular Biology
- Wound Healing Research
Background:
- Gastric ulcer healing involves complex molecular signaling.
- Trefoil peptides (rSP, rITF) and growth factors (EGF, TGFα) are implicated in mucosal repair.
Purpose of the Study:
- To investigate the temporal expression patterns of mRNAs encoding rSP, rITF, EGF, and TGFα in a rat gastric ulcer model.
- To elucidate the potential differential roles of trefoil peptides versus growth factors in gastric ulcer healing.
Main Methods:
- A rat model of gastric ulceration was induced using cryoprobe application.
- Messenger RNA (mRNA) expression levels were quantified using ribonuclease protection assays over 10 days.
- In situ hybridization was employed to localize rSP and rITF mRNA expression within gastric tissue.
Main Results:
- Ulceration triggered rapid induction of rSP and rITF mRNA.
- EGF and TGFα mRNA levels increased at later time points (3 and 6 days, respectively).
- Extensive rSP mRNA expression was observed in regenerating epithelia.
Conclusions:
- Trefoil peptides (rSP, rITF) exhibit distinct, rapid temporal expression patterns following gastric ulceration compared to EGF and TGFα.
- These findings suggest that trefoil peptides may play immediate, crucial roles in the early stages of gastric ulcer healing.