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骨关节炎和类风湿关节炎的滑膜细胞可产生纤溶酶原激活剂和纤溶酶原激活物抑制剂-1,并在其表面表达尿激酶型纤溶酶原激活剂受体。

Synoviocytes from osteoarthritis and rheumatoid arthritis produce plasminogen activators and plasminogen activator inhibitor-1 and display u-PA receptors on their surface.

作者信息

Cerinic M M, Generini S, Partsch G, Pignone A, Dini G, Konttinen Y T, Del Rosso M

机构信息

Institute of Internal Medicine IV, University of Florence, Italy.

出版信息

Life Sci. 1998;63(6):441-53. doi: 10.1016/s0024-3205(98)00293-8.

Abstract

The production of plasminogen activators and their inhibitors was studied in vitro in osteoarthritic (OA) and rheumatoid arthritic (RA) synovial fibroblasts (SF), obtained from RA and OA patients undergoing joint surgery. Subcultured SF were cultivated for 2, 4, 6, 8, 10 and 13 days and the medium assayed for the presence of both plasminogen activators (PAs) and plasminogen activator inhibitor-1 (PAI-1). The presence of urokinase-Plasminogen Activator (u-PA) receptors (u-PAR) on the surface of synovial cells was investigated by radio-ligand binding assay and cross-linking and by transmission electron microscopy (TEM) of a gold-u-PA complex. Our results showed a low production of tissue-type-Plasminogen Activator (t-PA) in both OA and RA SF, but relatively high levels of u-PA, until confluence, both in OA and in RA. SF were also able to produce plasminogen activator inhibitor in large amounts, in particular in RA since the very beginning of the culture. Receptors for u-PA were evident on both RA and OA SF. Our data show that SF in vitro produce mainly u-PA, the most important plasminogen activator involved in tissue modifications. The demonstration of u-PA receptors on the surface of OA and RA SF represents a step forward in the understanding of the possible role of fibrinolytic and tissue destructive proteinase cascade in joint inflammation.

摘要

对从接受关节手术的类风湿性关节炎(RA)和骨关节炎(OA)患者获取的滑膜成纤维细胞(SF),在体外研究了纤溶酶原激活剂及其抑制剂的产生情况。将传代培养的SF培养2、4、6、8、10和13天,并检测培养基中纤溶酶原激活剂(PAs)和纤溶酶原激活剂抑制剂-1(PAI-1)的存在情况。通过放射性配体结合测定、交联以及金-u-PA复合物的透射电子显微镜(TEM)观察,研究滑膜细胞表面尿激酶型纤溶酶原激活剂(u-PA)受体(u-PAR)的存在情况。我们的结果显示,OA和RA的SF中组织型纤溶酶原激活剂(t-PA)的产生量较低,但在OA和RA中,直至汇合时u-PA水平相对较高。SF也能够大量产生纤溶酶原激活剂抑制剂,尤其是在RA中,从培养一开始就是如此。RA和OA的SF上均明显存在u-PA受体。我们的数据表明,体外培养的SF主要产生u-PA,u-PA是参与组织重塑的最重要的纤溶酶原激活剂。OA和RA的SF表面存在u-PA受体,这在理解纤维蛋白溶解和组织破坏性蛋白酶级联反应在关节炎症中的可能作用方面向前迈进了一步。

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