OBJECTIVETo explore the effects of intestinal trefoil factor (ITF) on intestinal epithelial proliferation and its possible signal transduction mechanism.

METHODS1). The intestinal epithelial cytoplasmic membrane was isolated and harvested from Wistar rats, and it was treated with various doses of ITF in the concentration of 0.01, 0.10, 1.00 and 10.00 micro g/ml. The tyrosine protein kinase (TPK) activity from cytoplasmic membrane ITF receptor was determined by membrane-bound method. 2). The intestinal epithelial cells 6 (IEC-6) cultured in vitro were employed in the study. Some of the cells were used as normal control, while a group of cells were stimulated by 1 micro g/ml ITF, and others were treated by PD098059, SB202190 and SB202474, respectively. The last three agents were inhibitors of three members of mitogen-activated protein kinase family (MAPKs), i.e. extracellular signal regulated protein kinases (ERKs), protein kinase p38 (p38), and stress-activated protein kinase (SAPK). They were used before the addition of 1 micro g/ml of ITF. The changes in DNA synthetic rate and the MAPK activity of IEC-6 after being treated by above agents were assessed by (3)H-TdR incorporation method.

RESULTSITF receptor possessed TPK activity. TPK activity of ITF receptor, MAPKs activity and DNA synthetic rate of IEC-6 were increased obviously under the stimulation of ITF (P < 0.01). The above ITF effects could be evidently blocked by PD098059 and partially attenuated by SB202474. But SB202190 showed no effect in this respect.

CONCLUSIONITF could promote intestinal epithelial proliferation and transmit extracellular signals mainly by means of ERKs signalling pathway.