Transforming growth factor-beta and platelet derived growth factor regulation of fibrillar fibronectin matrix formation by synovial fibroblasts.
OBJECTIVE
To investigate factors regulating fibronectin fibrillar matrix formation by synovial fibroblasts.


METHODS
Basal and cytokine stimulated extracellular matrix (ECM) fibronectin produced by synovial fibroblasts was identified by immunofluorescence and Western blot. Alternative mRNA splicing of fibronectin was studied by reverse transcription polymerase chain reaction. The integrin receptor responsible for supporting fibronectin fibrillar matrix was identified by blocking antibodies and receptor levels studied by Western blot.


RESULTS
Transforming growth factor-beta (TGF-beta) or platelet derived growth factor (PDGF), but not interleukin 1 or exogenous fibronectin, induced ECM fibronectin. ECM fibronectin was blocked by the addition of antibody to the alpha5beta1 integrin. Cytokines did not significantly change alternative mRNA splicing of fibronectin or levels of alpha5beta1 integrin expression.


CONCLUSIONS
Synovial cell production of a fibrillar fibronectin matrix is induced by growth factors, including TGF-beta and PDGF. This induction is mediated by the alpha5beta1 integrin. Since fibrillar fibronectin formation was not strongly dependent on increased fibronectin or alpha5beta1 integrin levels, this effect may be mediated by growth factor induced changes in receptor affinity.
Sarkissian
M
M
Boston University School of Medicine, Arthritis Center, MA 02118, USA.
Lafyatis
R
R
D017398:Alternative Splicing; D018926:Anti-Allergic Agents / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism* / Q000494:pharmacology; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000276:immunology / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology; D010003:Osteoarthritis / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D017469:Receptors, Fibronectin / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology / Q000502:physiology; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D018926:Anti-Allergic Agents; D000911:Antibodies, Monoclonal; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D017469:Receptors, Fibronectin; D016201:Receptors, Lymphocyte Homing; D016212:Transforming Growth Factor beta