Altered collagen of human pathological fibroblasts impairs the synthesis of fibronectin.
Human fibroblasts with mutated type I collagen have marked defective adhesive capacities on exogenous type I collagen and exogenous fibronectin in comparison to normal fibroblasts. This defective cell adhesion could be partly explained by the decreased level of cell surface receptors of the beta 1-integrin family, i.e., the alpha 2 integrin subunit for type I collagen and the alpha 5 integrin subunit for fibronectin, observed in pathological fibroblasts. However, it appeared that the presence of altered collagen interfered both with fibronectin biosynthesis and with its surface expression. Using a binding assay on immobilized fibronectin, we demonstrated that the mutated collagen had a weaker binding to fibronectin. In addition, the pathological fibroblasts plated on a mixture of normal exogenous type I collagen and fibronectin exhibited the same maximal level of adhesion as control fibroblasts. These results indicate that fibroblasts with the mutated collagen exhibit a decreased binding to normal fibronectin, a modification of synthesis and surface expression of fibronectin, and, finally, altered adhesive capacities.
Lebbé
C
C
INSERM U180, Université René Descartes-Paris V, UFR Biomédicale des Saints-Pères, France.
Font
J
J
Bonaventure
J
J
Pichon
J
J
Wantyghem
J
J
Rossi
M
M
Haentjens
G
G
Cohen-Solal
L
L
Aubery
M
M
D002448:Cell Adhesion / Q000502:physiology; D003094:Collagen / Q000235:genetics / Q000502:physiology*; D005260:Female; D005333:Fetus; D005347:Fibroblasts / Q000473:pathology*; D005353:Fibronectins / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D009154:Mutation
D005353:Fibronectins; D003094:Collagen