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31 PRELIMINARY FINDINGS FROM DOWNREGULATION OF IEC EXPRESSION OF ILK IN VIVO B Salh, K Assi, D Owen, S Dedhar BACKGROUND: Integrins are transmembrane cell surface receptors that mediate cell-cell and cell-matrix contacts. Binding of ligands modulates a number of biological properties of cells through signal transduction. The recently identified integrin-linked kinase (ILK) is a binding partner of some integrins and has been ascribed essential roles in development and angiogenesis. It also imparts tumourigenic properties to cells when overexpressed.
Departments of Medicine, Pathology and Biochemistry, University of British Columbia, Vancouver, British Columbia
AIM: We were interested to explore its role in intestinal epithelial cells.
METHODS AND RESULTS: We used Fabp/Cre mice, which have the Cre recombinase expressed under the control of a modified Fabp promoter, and mated them with mice carrying a LoxP-flanked (floxed) ILK gene (ILKflox/flox). (These mice have been used to demonstrate ILK's effects on chondrocytes as well as its role in vascular development.) Expression of Cre and excision of ILK were determined in the offspring using PCR. We observed that mice with intestinal epithelial cell ILK knockout developed normally to the end of the monitoring period (one year). They exhibited partial reduction in the size of the caecum (approximately 70% of littermate size). They did not exhibit any macroscopic signs of basally increased inflammation. Immunohistochemical analysis revealed that there was diminished ILK expression in knockout animals. Evaluation of PCNA and BrDU in the knockout animals revealed a significant reduction in these parameters as compared with the wild-type animals. Previous work has identified PKB and possibly GSK3 as being potential targets of ILK, however, we did not observe any changes in the expression or activation of these markers. We examined the influence of ILK reduction on E-cadherin expression and observed a reduction in cell membranes staining with this. Notably, we observed an increase in the number of apoptotic cells both in the distal small bowel and colon.
CONCLUSION: We conclude that ILK has a role in intestinal epithelial cell proliferation and fate, and that this model may be useful for the investigation of the role of ILK in intestinal disorders.