Document Detail

Differences in extracellular matrix production and basic fibroblast growth factor response in skin fibroblasts from sporadic and familial Alzheimer's disease.
MedLine Citation:
PMID:  17660861     Owner:  NLM     Status:  MEDLINE    
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.
Catia Bellucci; Cinzia Lilli; Tiziano Baroni; Lucilla Parnetti; Sandro Sorbi; Carla Emiliani; Eleonora Lumare; Paolo Calabresi; Stefania Balloni; Maria Bodo
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular medicine (Cambridge, Mass.)     Volume:  13     ISSN:  1076-1551     ISO Abbreviation:  Mol. Med.     Publication Date:    2007 Sep-Oct
Date Detail:
Created Date:  2007-10-12     Completed Date:  2007-12-06     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  9501023     Medline TA:  Mol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  542-50     Citation Subset:  IM    
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
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MeSH Terms
Alzheimer Disease / classification,  metabolism*,  pathology
Case-Control Studies
Cell Culture Techniques
Cells, Cultured
Collagen / biosynthesis,  genetics
Extracellular Matrix / metabolism*
Extracellular Matrix Proteins / biosynthesis,  genetics
Fibroblast Growth Factor 2 / genetics,  metabolism,  pharmacology*
Fibroblasts / drug effects*
Gene Expression
Glycosaminoglycans / biosynthesis,  genetics
Matrix Metalloproteinase 1 / biosynthesis,  genetics
Proteoglycans / biosynthesis,  genetics
RNA, Messenger / metabolism
Skin / cytology*
Reg. No./Substance:
0/Extracellular Matrix Proteins; 0/Glycosaminoglycans; 0/Proteoglycans; 0/RNA, Messenger; 103107-01-3/Fibroblast Growth Factor 2; 9007-34-5/Collagen; EC Metalloproteinase 1

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