Abstract
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.
Highlights
Integrins are a family of heterodimeric transmembrane adhesion molecules comprised of non-covalently associated ␣- and -subunits
Developmental differences in ␣v-integrin utilization are addressed by comparing the responses of adult and fetal -cells, and vitronectin is used as a substrate based on its unique pattern of expression in the developing pancreas
Following extracellular matrix (ECM) sequestration, VN can regulate a variety of cellular processes including migration, differentiation, proliferation, and morphogenesis [15, 16] Importantly, VN expression has recently been confirmed in the developing human pancreas in association with both epithelial cells and insulin-expressing cells emerging from the ductal epithelium [17]
Summary
Integrins are a family of heterodimeric transmembrane adhesion molecules comprised of non-covalently associated ␣- and -subunits. Following ECM sequestration, VN can regulate a variety of cellular processes including migration, differentiation, proliferation, and morphogenesis [15, 16] Importantly, VN expression has recently been confirmed in the developing human pancreas in association with both epithelial cells and insulin-expressing cells emerging from the ductal epithelium [17]. Based on this highly restricted distribution it is suggested that endocrine progenitors may arise from a larger pool of VN-producing cells [17]. ␣v-Integrins and -Cell Function which can disrupt ␣v-integrin ligation, has been shown to prevent normal islet development in vivo [17]
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