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Extracellular matrix protects pancreatic beta-cells against apoptosis: role of short- and long-term signaling pathways

Maedler, Kathrin
Donath, Marc
Published in Diabetes. 2004, vol. 53, no. 8, p. 2034-2041
Abstract We have shown previously that culture of beta-cells on matrix derived from 804G cells and rich in laminin-5 improves their function. The purpose of this study was to investigate whether this matrix protects beta-cells against apoptosis and to elucidate signaling pathways involved. Matrix protected sorted rat beta-cells against apoptosis under standard conditions (11.2 mmol/l glucose, 10% serum), after serum deprivation (1% serum), and in response to interleukin-1beta (IL-1beta; 2 ng/ml), compared with control (poly-L-lysine [pLL]). Caspase-8 activity was reduced in cells cultured on matrix, whereas focal adhesion kinase (FAK), protein kinase B (PKB, or Akt), and extracellular signal-regulated kinase (ERK) phosphorylation was augmented. Treatment (4 h) with an anti-beta1 integrin antibody, with the ERK pathway inhibitor PD98059, and/or with the phosphatidylinositol 3-kinase inhibitor LY294002 augmented cell death on 804G matrix but not on pLL. In long-term assays (48 h), PD98059 but not LY294002 drastically augmented cell death on 804G matrix but did so to a lesser extent on pLL. The protein inhibitor of nuclear factor-kappaB (IkappaBalpha) was overexpressed in cells cultured 18 h on matrix with partial blockade by PD98059. In summary, this study provides evidence for activation of signaling pathways and gene expression by extracellular matrix leading to improved beta-cell survival.
Keywords AnimalsApoptosis/drug effects/ physiologyCaspase 8Caspases/metabolismCulture MediaCulture Media, Serum-FreeExtracellular Matrix/ physiologyFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesInterleukin-1/pharmacologyIslets of Langerhans/ cytology/drug effectsMitogen-Activated Protein Kinases/metabolismPolylysine/pharmacologyProtein-Serine-Threonine Kinases/metabolismProtein-Tyrosine Kinases/metabolismProto-Oncogene Proteins/metabolismProto-Oncogene Proteins c-aktRatsSignal Transduction
PMID: 15277383
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Research groups Fonction de l'îlot de Langerhans (324)
La transplantation d'îlots de Langerhans (623)
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HAMMAR BOUVERET, Eva et al. Extracellular matrix protects pancreatic beta-cells against apoptosis: role of short- and long-term signaling pathways. In: Diabetes, 2004, vol. 53, n° 8, p. 2034-2041. doi: 10.2337/diabetes.53.8.2034 https://archive-ouverte.unige.ch/unige:8792

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Deposited on : 2010-07-12

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