Role of TFF in healing of stress-induced gastric lesions

Abstract

Aim: To determine the changes of pS2 and ITF of TFF expression in gastric mucosa and the effect on ulcer healing of pS2, ITF to Water-immersion and restraint stress (WRS) in rats.

Methods: Wistar rats were exposed to single or repeated WRS for 4 h every other day for up to 6 days.Gastric mucosal blood flow (GMBF) was measured by LDF-3 flowmeter and the extent of gastric mucosal lesions were evaluated grossly and histologically. Expression of pS2 and ITF mRNA was determined by RT-PCR. Immunohistochemistry was used to further detect the expression of pS2 and ITF.

Results: WRS applied once produced numerous gastric mucosal erosions, but the number of these lesions gradually declined and GMBF restored at 2, 4, 8 h after stress. The area of gastric mucosal lesion was reduced by 64.9 % and GMBF was increased by 89.8 % at 8 h. The healing of stress-induced ulcerations was accompanied by increased expression of pS2 (0.51+/-0.14 vs 0.77+/-0.11, P<0.01) and ITF (0.022+/-0.001 vs 0.177+/-0.010, P<0.01). The results were demonstrated further by immunohistochemistry of pS2 (0.95+/-0.11 vs 1.41+/-0.04, P<0.01) and ITF (0.134+/-0.001 vs 0.253+/-0.01,P<0.01). With repeated WRS, adaptation to this WRS developed, the area of gastric mucosal lesions was reduced by 22.0 % after four consecutive WRS. This adaptation to WRS was accompanied by increased GMBF (being increased by 94.2 %), active cell proliferation in the neck region of gastric glands, and increased expression of pS2 (0.37+/-0.02 vs 0.77+/-0.01, P<0.01) and ITF (0.040+/- 0.001 vs 0.372+/-0.010, P<0.01). The result was demonstrated further by immunohistochemistry of pS2 (0.55+/-0.04 vs 2.46+/-0.08, P<0.01) and ITF (0.134+/-0.001 vs 0.354+/-0.070, P<0.01).

Conclusion: TFF may not only participate in the early phase of epithelial repair known as restitution (maked by increased cell migration), but also play an important role in the subsequent, protracted phase of glandular renewal(made by cell proliferation).

Figure 1

Necrosis appeared as craters in rats after exposed to single WRS for 4 h (HE×200).

Figure 2

Foveolae and neck region elongated and the mucosa appeared thicker after rats exposed to 4^th WRS for 4 h(HE×400).

Figure 3

Messenger RNA expression of pS₂ mRNA and β-ac-tin in gastric mucosa of rats after single exposure to WRS and in control intact rats (M = PCR size marker, 1 = control group, 2 = group 1, 3 = group 2, 4 = group 3, 5 = group 4).

Figure 4

Messenger RNA expression of ITF mRNA and β-actin in gastric mucosa of rats after single exposure to WRS and in control intact rats (M = PCR size marker, 1 = control group, 2 = group 1, 3 = group 2, 4 = group 3, 5 = group 4).

Figure 5

Messenger RNA expression of pS₂ mRNA and β-actin in gastric mucosa of rats after repeated exposure to WRS and in control intact rats (M = PCR size marker, 1 = control group, 2 = group I, 3 = group II, 4 = group III, 5 = group IV).

Figure 6

Messenger RNA expression of ITF mRNA and β-actin in gastric mucosa of rats after repeated exposure to WRS and in control intact rats (M = PCR size marker, 1 = control group, 2 = group I, 3 = group II, 4 = group III, 5 = group IV).