Mucosal expression of p21, p27, p53, Bcl-2, and bax after small bowel resection and autotransplantation in pigs.
Massive small bowel resection increases ileal villus height as part of normal adaptation. However, despite no gut loss, autotransplantation of the entire small intestine also increases ileal villus height. Our aim was to test whether similar modulation of enterocyte proliferation and apoptosis underpin these comparable increases in villus height. Fifteen pigs were randomly assigned for laparotomy (n=5), 75% proximal small bowel resection (n=5), or jejunoileal autotransplantation (n=5). Eight weeks postoperatively, full-thickness small bowel sections underwent routine immunohistochemistry for cell cycle inhibitors (p53, p21, and p27), antiapoptotic Bcl-2, and proapoptotic bax. The specimens were analyzed semiquantitatively, and the number of intensively positive epithelial cells for each group was compared from 20 digital images (0.32 mm(2)/image). Compared with laparotomy, small bowel resection decreased the number of p27-positive enterocytes in both jejunum and ileum, increased the number of bax-expressing cells in ileum, but decreased the number of bax-expressing cells in jejunum. In contrast, compared with laparotomy, jejunoileal autotransplantation altered neither mucosal bax nor p27 expression. In all groups, Bcl-2 expression was similarly confined to inflammatory cells of the lamina propria, while both p53 and p21 were negative. We conclude that long-term alterations in the enterocytic expression of certain cell cycle and apoptosis markers (p27 and bax) accompany small bowel resection. These changes differ between the jejunum and the ileum and are not seen after whole small bowel autotransplantation. Therefore, increased ileal villus height after autotransplantation, despite resembling postresectional intestinal adaptation, is underpinned by different regulation of enterocyte proliferation and apoptosis.
Lauronen
Jouni
J
Transplantation Laboratory, Haartman Institute, University of Helsinki, Haartmaninkatu 3, P.O. Box 21, 00014 Helsinki, Finland. Jouni.Lauronen@helsinki.fi
Pakarinen
Mikko P
MP
Halttunen
Jorma
J
Kuusanmäki
Pekka
P
Haglund
Caj
C
Paavonen
Timo
T
D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D007082:Ileum / Q000637:transplantation*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000601:surgery*; D007583:Jejunum / Q000637:transplantation*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011897:Random Allocation; D018709:Statistics, Nonparametric; D013552:Swine; D014182:Transplantation, Autologous; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27