Abstract
Integrin-linked kinase (ILK) plays a role in integrin signaling-mediated extracellular matrix (ECM)–cell interactions and also acts as a scaffold protein in functional focal adhesion points. In the present study, we investigated the expression and roles of ILK in human intestinal epithelial cells (IECs) in vivo and in vitro. Herein, we report that ILK and its scaffold-function interacting partners, PINCH-1, α-parvin, and β-parvin, are expressed according to a decreasing gradient from the bottom of the crypt (proliferative/undifferentiated) compartment to the tip of the villus (non-proliferative/differentiated) compartment, closely following the expression pattern of the ECM/basement membrane component fibronectin. The siRNA knockdown of ILK in human IECs caused a loss of PINCH-1, α-parvin, and β-parvin expression, along with a significant decrease in cell proliferation via a loss of cyclin D1 and an increase in p27 and hypophosphorylated pRb expression levels. ILK knockdown severely affected cell spreading, migration, and restitution abilities, which were shown to be directly related to a decrease in fibronectin deposition. All ILK knockdown-induced defects were rescued with exogenously deposited fibronectin. Altogether, our results indicate that ILK performs crucial roles in the control of human intestinal cell and crypt–villus axis homeostasis—especially with regard to basement membrane fibronectin deposition—as well as cell proliferation, spreading, and migration. J. Cell. Physiol. 222: 387–400, 2010. © 2009 Wiley-Liss, Inc.
Highlights
The dynamic renewal of the intestinal epithelium is essentially characterized by intestinal epithelial cell (IEC) production and maturation in the crypts, migration out of the crypts onto the base of the villi and, thereafter, further migration of differentiated cells to the tip of the villi where they are shed by anoıkis (Crosnier et al, 2006)
Integrin-linked kinase (ILK) was found to be localized at the basal plasma membrane of the intestinal epithelium along the entire length of the crypt–villus axis, but in a clear expression gradient with stronger ILK staining in the crypt compartment than in the villus (Fig. 1A)
We report that the expression patterns of ILK, PINCH-1, a-parvin, and bparvin along the crypt–villus axis decreased as a function of enterocytic differentiation and followed the basement membrane (BM) distribution of fibronectin, that is, being largely predominant in human proliferative/undifferentiated crypt IECs
Summary
Some ECM components, such as type IV collagen and the laminins, are exclusive to BMs (Laurie et al, 1982; SimonAssmann et al, 1986; Beaulieu and Vachon, 1994; Beaulieu, 1997) In the intestine, these molecules are differentially expressed along the crypt–villus axis and are believed to perform distinct roles in IEC processes (SimonAssmann et al, 1986; Beaulieu, 1997). These molecules are differentially expressed along the crypt–villus axis and are believed to perform distinct roles in IEC processes (SimonAssmann et al, 1986; Beaulieu, 1997)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
