EGF and TGF-beta1 gene expression in chronically rejecting small bowel transplants.
Long-term survival of small bowel transplants is hampered by chronic rejection. Epidermal growth factor (EGF) and transforming growth factor beta (TGF-beta) have opposing, regulatory roles in normal intestinal physiology and may be involved in the pathogenesis of chronic intestinal rejection. Our aim was to investigate the expression of EGF and TGF-beta1 in chronically rejecting small bowel transplants. Orthotopic small bowel transplantation was performed in the allogeneic DA-to-AS rat combination; Cyclosporin was administered temporarily to prevent acute rejection. Controls were DA isografts and normal DA rats. PreproEGF and TGF-beta1 gene expression was evaluated by northern blot analysis of the ileum RNA and standardized against glyceraldehyde-3-phosphate-dehydrogenase expression. Allografts demonstrated functional impairment and histological features of chronic rejection, whereas isografts appeared normal. Allografts demonstrated a significant reduction of EGF mRNA when compared to DA isografts. No significant changes were detected in TGF-beta1 expression in either allogeneic or syngeneic grafts. In conclusion, this study demonstrates reduced preproEGF and preserved TGF-beta1 gene expression in chronically rejecting small bowel transplants.
Kouwenhoven
E A
EA
Department of Medicine, Monash Medical School, Melbourne, Victoria, Australia.
Stein-Oakley
A N
AN
Jablonski
P
P
de Bruin
R W
RW
Thomson
N M
NM
D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern / Q000379:methods / Q000706:statistics & numerical data; D002908:Chronic Disease; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000032:analysis / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006084:Graft Rejection / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D007421:Intestine, Small / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000502:physiology*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor