Alphav-integrin Utilization in Human Beta-Cell Adhesion, Spreading, and Motility

J Biol Chem. 2004 Apr 23;279(17):17731-7. doi: 10.1074/jbc.M308425200. Epub 2004 Feb 6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blotting, Western
  • Cadaver
  • Cell Adhesion
  • Cell Line
  • Cell Movement
  • Collagenases / metabolism
  • Down-Regulation
  • Flow Cytometry
  • Gene Expression Regulation, Developmental
  • Humans
  • Integrin alphaV / metabolism
  • Integrin alphaV / physiology*
  • Integrins / metabolism
  • Islets of Langerhans / cytology*
  • Microscopy, Fluorescence
  • Middle Aged
  • Pancreas / cytology
  • Pancreas / embryology
  • Precipitin Tests
  • Protein Binding
  • Receptors, Vitronectin / metabolism
  • Time Factors
  • Vitronectin / metabolism

Substances

  • Integrin alphaV
  • Integrins
  • Receptors, Vitronectin
  • Vitronectin
  • integrin alphaVbeta5
  • integrin alphavbeta1
  • Collagenases