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Submitted on October 1, 2004
Accepted on December 13, 2004
1 integrin receptors during rat pancreas development - sites and dynamics
Departments of Physiology & Pharmacology, Medicine, University of Western Ontario, London, Department of Physiology, University of Toronto, Ontario, Canada
* To whom correspondence should be addressed. E-mail: rwang{at}uwo.ca.
The integrin receptors link to extracellular matrix proteins and exert a dynamic role in development by providing the physical basis for cell adhesion and controlling cell growth. In the present study, we examined changes in the expression of
1 integrins and it's associated
subunits to islet cell development in the rat pancreas. A significant increase in protein expression of integrin
3,
6 and
1 was observed from fetal to postnatal life. High mRNA levels of these integrin subunits was detected at embryonic day 18 and dropped significantly after birth with relatively low expression throughout postnatal life. Integrins
3,
5,
6 and
1 were expressed in a cell-specific manner in the pancreas with high integrin immunoreactivity in duct and islet regions during fetal life, and a progressive increase later into postnatal life. The co-expression with islet and putative islet precursor markers during fetal and postnatal development suggest a role for these integrin subunits in differentiation and maturation of islets. Functional studies in vitro showed that anti-
1 antibody treatment inhibited islet cell adhesion to extracellular matrices and disrupted islet architecture. Blockade of
1 integrin receptor and knockdown
1 mRNA resulted in a decrease in the expression of insulin mRNA and increased islet cell death. These results suggest that progression in islet cell development is accompanied by and dependent upon cell adhesion via
1 integrin and it's respective
subunits and suggest that the
1 family of integrins may play a critical role in islet cell architecture, development, integrity and function.
1 integrin blocking antibody
1 integrin siRNA
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