期刊
JOURNAL OF IMMUNOLOGY
卷 175, 期 7, 页码 4555-4560出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.175.7.4555
关键词
-
类别
资金
- NCRR NIH HHS [3M01-RR-02558-12S1, M01RR02558] Funding Source: Medline
- NIAMS NIH HHS [R01AR46718, IP50AR44888, 1R03AR050517-01A2] Funding Source: Medline
Fibroblasts from patients with systemic sclerosis (SSc) are activated producing excessive amounts of extracellular matrix (ECM) components. Recently, we identified a new SSc-specific autoantibody against portions of fibrillin-1, a major component of ECM microfibrils and regulator of TGF-beta 1 signaling. To examine a potential pathogenic role of anti-fibrillin-1 autoantibodies, normal human fibroblasts were treated with affinity-purified autoantibodies isolated from SSc sera and then examined for alterations in gene and protein expression levels using microarrays, quantitative RT-PCR, immunoblots, and immunofluorescence. Compared with fibroblasts cultured in normal medium or in medium containing normal human IgG, anti-fibrillin-1 autoantibody-treated normal dermal fibroblasts showed increased expression of COL and several other ECM components characteristically overexpressed in SSc fibroblasts. This was accompanied by phosphorylation and nuclear translocation of Smad3. Neutralization of TGF-beta 1 with anti-TGF-beta 1 Abs significantly diminished the activation of fibroblasts by anti-fibrillin-1 autoantibodies. These data indicate that anti-fibrillin-1 autoantibodies can induce the activation of normal dermal fibroblasts into a profibrotic phenotype resembling that of SSc by potentially causing the release of sequestered TGF-beta 1 from fibrillin-1-containing microfibrils in the ECM.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据