Expression of peptide transporter following intestinal transplantation in the rat.
BACKGROUND
The absorptive function of the intestinal graft is one of the most important factors for successful intestinal transplantation. To clarify whether the intestinal H(+)/peptide cotransporter (PEPT1) was expressed in the transplanted intestine, we examined the expression of PEPT1 in an experimental model of rat small intestinal transplantation in comparison with expression of Na(+)/glucose cotransporter (SGLT1).


METHODS
Heterotopic intestinal transplantation was performed in allogeneic and syngeneic rat strain combinations. An additional group of allogeneic recipients was treated with tacrolimus (1 mg/kg) prior to transplantation, then daily for 7 days. Intestinal grafts were examined for histopathology and PEPT1 and SGLT1 expression.


RESULTS
In the isografts, the levels of messenger RNA (mRNA) encoding both transporters were not changed, while the amount of SGLT1 protein was decreased and that of PEPT1 protein was increased. In the allografts, mRNA level and protein amount of both transporters and the amount of villin protein were decreased, and microscopic examination revealed histopathological features of rejection on day 7. Tacrolimus treatment ameliorated the histopathological features and prevented the decrease in villin protein expression. However, the decreases in PEPT1 and SGLT1 expression (both mRNA and protein) were partially prevented by tacrolimus treatment.


CONCLUSIONS
This study indicated that the expression of transporters should be determined to evaluate intestinal graft function in addition to histopathological examination of the mucosa and that the levels of mRNA encoding intestinal nutrient transporters in biopsy specimens may be useful for evaluating the intestinal graft function for intestinal transplant patients.
Motohashi
H
H
Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, USA.
Masuda
S
S
Katsura
T
T
Saito
H
H
Sakamoto
S
S
Uemoto
S
S
Tanaka
K
K
Inui
K I
KI
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics*; D015870:Gene Expression; D006084:Graft Rejection / Q000188:drug therapy / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007583:Jejunum / Q000737:chemistry / Q000473:pathology / Q000637:transplantation*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000235:genetics; D000074011:Peptide Transporter 1; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D051269:Sodium-Glucose Transporter 1; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis; D027981:Symporters; D016559:Tacrolimus / Q000494:pharmacology
D002352:Carrier Proteins; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D000074011:Peptide Transporter 1; D012333:RNA, Messenger; C489940:Slc15a1 protein, rat; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D027981:Symporters; D000254:Sodium-Potassium-Exchanging ATPase; D016559:Tacrolimus