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Molecular Medicine

, Volume 13, Issue 9–10, pp 542–550 | Cite as

Differences in Extracellular Matrix Production and Basic Fibroblast Growth Factor Response in Skin Fibroblasts from Sporadic and Familial Alzheimer’s Disease

  • Catia Bellucci
  • Cinzia Lilli
  • Tiziano Baroni
  • Lucilla Parnetti
  • Sandro Sorbi
  • Carla Emiliani
  • Eleonora Lumare
  • Paolo Calabresi
  • Stefania Balloni
  • Maria Bodo
Research Article

Abstract

Extracellular matrix (ECM) molecules and growth factors, such as fibroblast growth factor (FGF), play a crucial role in Alzheimer’s disease (AD). The purpose of this investigation was to determine whether phenotypic alterations in ECM production are present in non-neuronal AD cells associated with different FGF expression and response. Synthesis of glycosaminoglycans (GAG) and collagen were measured in skin fibroblasts from patients with familial, sporadic AD (FAD and SAD respectively), and from age-matched controls by radiolabeled precursors. Proteoglycans (PG), metalloprotease (MMP)-1, and FGF gene expressions were measured by reverse transcription-polymerase chain reaction. The results showed different ECM neosynthesis and mRNA levels in the two AD fibroblast populations. FAD accumulated more collagen and secreted less GAG than SAD. Biglycan PG was upregulated in FAD while betaglycan, syndecan, and decorin were markedly downregulated in SAD fibroblasts. We found a significant decrease of MMP1, more marked in FAD than in SAD fibroblasts. Constitutive FGF expression was greatly reduced in both pathological conditions (SAD > FAD). Moreover, an inverse high affinity/low affinity FGF receptor ratio between SAD and FAD fibroblasts was observed. FGF treatment differently modulated ECM molecule production and gene expression in the two cell populations. These observations in association with the changes in FGF gene expression and in the FGF receptor number, suggest that cellular mechanisms downstream from FGF receptor binding are involved in the two different forms of AD.

Notes

Acknowledgments

Supported by fundings from the University of Perugia, by the Italian Ministry of Instruction, University and Research (Grant 2005051707–005 and 2005062887–004) and by the Cassa di Risparmio of Florence (Grant 2003.1764).

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Copyright information

© Feinstein Institute for Medical Research 2007

Authors and Affiliations

  • Catia Bellucci
    • 1
  • Cinzia Lilli
    • 1
  • Tiziano Baroni
    • 1
  • Lucilla Parnetti
    • 2
  • Sandro Sorbi
    • 3
  • Carla Emiliani
    • 1
  • Eleonora Lumare
    • 4
  • Paolo Calabresi
    • 2
  • Stefania Balloni
    • 1
  • Maria Bodo
    • 2
  1. 1.Department of Experimental Medicine and Biochemical SciencesUniversity of PerugiaPerugiaItaly
  2. 2.Department of Specialistic Medicine and Public Health, Neuroscience Clinical sectionUniversity of PerugiaPerugiaItaly
  3. 3.Department of Neurologic and Psychiatric SciencesUniversity of FirenzeFirenzeItaly
  4. 4.Forensic Medicine InstituteUniversity of PerugiaPerugiaItaly

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