Alphav-integrin utilization in human beta-cell adhesion, spreading, and motility.
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.
Kaido
Thomas
T
Islet Research Laboratory at The Whittier Institute for Diabetes, Department of Pediatrics, The University of California at San Diego, La Jolla, California 92037, USA.
Perez
Brandon
B
Yebra
Mayra
M
Hill
Jesse
J
Cirulli
Vincenzo
V
Hayek
Alberto
A
Montgomery
Anthony M
AM
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002102:Cadaver; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D017364:Collagenases / Q000378:metabolism; D015536:Down-Regulation; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism / Q000502:physiology*; D016023:Integrins / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010179:Pancreas / Q000166:cytology / Q000196:embryology; D011233:Precipitin Tests; D011485:Protein Binding; D019030:Receptors, Vitronectin / Q000378:metabolism; D013997:Time Factors; D019096:Vitronectin / Q000378:metabolism
D039564:Integrin alphaV; D016023:Integrins; D019030:Receptors, Vitronectin; D019096:Vitronectin; C064660:integrin alphaVbeta5; C094340:integrin alphavbeta1; D017364:Collagenases