αv-Integrin utilization in human β-cell adhesion, spreading, and motility

被引:58
作者
Kaido, T [1 ]
Perez, B [1 ]
Yebra, M [1 ]
Hill, J [1 ]
Cirulli, V [1 ]
Hayek, A [1 ]
Montgomery, AM [1 ]
机构
[1] Univ Calif San Diego, Dept Pediat, Whittier Inst Diabet, Islet Res Lab, La Jolla, CA 92037 USA
关键词
D O I
10.1074/jbc.M308425200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The role of individual integrins in human beta-cell development and function is largely unknown. This study describes the contribution of alpha(v)-integrins to human beta-cell adhesion, spreading, and motility. Developmental differences in alpha(v)-integrin utilization are addressed by comparing the responses of adult and fetal beta-cells, and vitronectin is used as a substrate based on its unique pattern of expression in the developing pancreas. Fetal and adult beta-cells attached equally to vitronectin and integrin alpha(v)beta(5) was found to support the adhesion of both mature and immature beta-cell populations. Fetal beta-cells were also observed to spread and migrate on vitronectin, and integrin alpha(v)beta(1) was found to be essential for these responses. In contrast to their fetal counterparts, adult beta-cells failed to either spread or migrate and this deficit was associated with a marked down-regulation of alpha(v)beta(1) expression in adult islet preparations. The integrin alpha(v)beta(3) was not found to support significant beta-cell attachment or migration. Based on our findings, we conclude that integrins alpha(v)beta(5) and alpha(v)beta(1) are important mediators of human beta-cell adhesion and motility, respectively. By supporting fetal beta-cell migration, alpha(v)beta(1) could play an important role in early motile processes required for islet neogenesis.
引用
收藏
页码:17731 / 17737
页数:7
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