Sarkissian M, Lafyatis R
Boston University School of Medicine, Arthritis Center, MA 02118, USA.
J Rheumatol. 1998 Apr;25(4):613-22.
To investigate factors regulating fibronectin fibrillar matrix formation by synovial fibroblasts.
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.
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.
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.
研究调节滑膜成纤维细胞纤连蛋白纤维状基质形成的因素。
通过免疫荧光和蛋白质印迹法鉴定滑膜成纤维细胞产生的基础和细胞因子刺激的细胞外基质（ECM）纤连蛋白。通过逆转录聚合酶链反应研究纤连蛋白的可变mRNA剪接。通过阻断抗体鉴定负责支持纤连蛋白纤维状基质的整合素受体，并通过蛋白质印迹法研究受体水平。
转化生长因子-β（TGF-β）或血小板衍生生长因子（PDGF），而非白细胞介素1或外源性纤连蛋白，可诱导ECM纤连蛋白。添加针对α5β1整合素的抗体可阻断ECM纤连蛋白。细胞因子并未显著改变纤连蛋白的可变mRNA剪接或α5β1整合素表达水平。
滑膜细胞产生纤维状纤连蛋白基质是由包括TGF-β和PDGF在内的生长因子诱导的。这种诱导是由α5β1整合素介导的。由于纤维状纤连蛋白的形成并不强烈依赖于纤连蛋白或α5β1整合素水平的增加，这种效应可能是由生长因子诱导的受体亲和力变化介导的。
