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Expression of ß1 Integrin Receptors during Rat Pancreas Development—Sites and Dynamics

Departments of Physiology and Pharmacology (N.K.Y., J.L., R.W.) and Medicine (R.W.), University of Western Ontario, London, Ontario, Canada N6C 2V5; and Department of Physiology, University of Toronto (M.B.W.), Toronto, Ontario, Canada M5S 1A8

Address all correspondence and requests for reprints to: Dr. Rennian Wang, Victoria Research Laboratories Room A5 140, 800 Commissioners Road, East London, Ontario, Canada N6C 2V5. 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 ß1 integrins and its associated -subunits to islet cell development in the rat pancreas. A significant increase in protein expression of integrin 3, 6, and ß1 was observed from fetal to postnatal life. High mRNA levels of these integrin subunits was detected at embryonic d 18 and dropped significantly after birth with relatively low expression throughout postnatal life. Integrins 3, 5, 6, and ß1 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 coexpression 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-ß1 antibody treatment inhibited islet cell adhesion to extracellular matrices and disrupted islet architecture. Blockade of ß1 integrin receptor and knockdown ß1 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 ß1 integrin and its respective -subunits and suggest that the ß1 family of integrins may play a critical role in islet cell architecture, development, integrity, and function.

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