The Physiological Role of Transforming Growth Factor-Beta in Gastrointestinal Development in the Pig
Author: Jie Mei, 梅節
Publisher: Open Dissertation Press
Release Date: January 27, 2017
This dissertation, "The Physiological Role of Transforming Growth Factor-beta in Gastrointestinal Development in the Pig" by Jie, Mei, 梅節, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author.
Abstract of thesis entitled
THE PHYSIOLOGICAL ROLE OF TRANSFORMING GROWTH FACTOR-BETA IN GASTROINTESTINAL DEVELOPMENT IN THE PIG
for the degree of Doctor of Philosophy at The University of Hong Kong in April 2004
Transforming growth factor-beta (TGF-β) has been detected in the milk of various species, including the pig. The concentration of TGF-β in the colostrum is particularly high. It has been speculated that milk-borne TGF-β may play a role in the postnatal adaptation of the gastrointestinal tract in suckling animals. However, a prerequisite for any physiological effects of milk-borne TGF-β in suckling animals is the presence of TGF-β receptors in the mucosa of the intestine. The objectives of the present study were to investigate (i) the developmental changes of TGF-β receptors in the intestinal mucosa in foetal and neonatal pigs, (ii) the effects of intestinal exposure to milk-borne TGF-β on intestinal TGF-β receptor expression, and (iii) the changes of endogenous expression of TGF-β in the intestinal mucosa of neonatal pigs in association with weaning.
Western blot analysis and immunohistochemical staining showed the presence of the three types of TGF-β receptors (RI, RII and RIII) along the small intestine in foetal and postnatal pigs. In foetal pigs of 90 and 105 days of gestation, the receptors were predominantly localized at the intestinal crypts. At birth, the staining of the three receptors shifted from the crypts to the apical membrane of the villus epithelium. Following suckling, there was a transient decline in RI and RII density in the villus epithelium but a marked increase in positively-stained lymphocytes in the lamina propria of the intestine. In 21-day-old pre-weaning pigs, the staining of RI and RII shifted from the apical side of the villus epithelium to the basolateral side, and the intensity of RIII decreased significantly.
To investigate if the transient decline of TGF-β receptor intensity in the small intestine in suckling piglets was due to the exposure of the intestine to milk-borne TGF-β, foetal and newborn pigs were administered with colostrum, milk, infant formula, amniotic fluid or water. It was observed that the immunostaining intensity of TGF-β receptors was obviously down-regulated in the villus tips of the small intestine when piglets were fed with colostrum which is known to contain high level of TGF-β., while intensive staining for the receptors was seen at the basal membrane of the villus epithelium in newborn piglets fed with milk, infant formula or water. No obvious differences in the distribution and the staining intensity of TGF-β receptors in the foetal small intestine were observed between the treatment groups.
This study also showed that the level of TGF-β1 at the intestinal villus epithelium decreased significantly, while the number of leukocytes positively-stained with TGF-β1 antibodies increased significantly, in pigs four days after weaning. The level of TGF-β1 at the intestinal epithelium returned to the pre-weaning value by the eighth day of post-weaning. The transient decrease of TGF-β1 level at the intestinal villus epithelium was associated with obvious intestinal villus atrophy and a marked reduction of mucosal digestive enzyme activities.
The above findings support the hypothesis that TGF-β plays a signif