...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Expression and function of wingless and frizzled homologs in rheumatoid arthritis
【24h】

Expression and function of wingless and frizzled homologs in rheumatoid arthritis

机译：类风湿关节炎中无翅和卷曲的同系物的表达和功能

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Rheumatoid arthritis (RA) is accompanied by synovial inflamma- tion. proliferation, and cartilage destruction. The reasons the activation of synovial fibroblasts often persists despite antiinflam- matory therapy are not known. One possibility is that the synovial membrane becomes gradually repopulated with immature mesen- chymal and bone marrow cells with altered properties. To explore this hypothesis. we have investigated the expression in RA syno- vial tissues of various embryonic growth factors from the wingless (wnt) and frizzled (fz) families, which have been implicated in cell-fate determination in both bone marrow progenitors and limb-bud mesenchyme. Reverse transcriptase--PCR analysis re- vealed expression of five wnt (wntt. 5a, 10b, 1 f. and 13) and three fz (fz2, i and 7) isoforms in RA synovial tissues. Osteoarthritis synovial tissues expressed much less wn t58 and fz5. Northern blotting confirmed the overexpression of wnt5a and fz5 in RA synovial tissues, in comparison to a panel of normal adult tissues. Compared with normal synovial fibroblasts, cultured RA fibroblast- like synoviocytes expressed higher levels of lL-6, lL-8. and lL-1S. Transfection of normal fibroblasts with a wnt5a expression vector reproduced this pattern of cytokine expression and stimulated IL-1 S secretion. These results suggest that the unusual phenotypic properties of RA fibroblasts may be attributable partly to their replacement with primitive fibroblast-like synoviocytes with char- acteristics of immature bone marrow and mesenchymal cells. Clear delineation of the signaling pathway(s) initiated by the wn t5a/fzS ligand--receptor pair in the RA synovium may yield new targets for therapeutic intervention.
机译：类风湿关节炎（RA）伴有滑膜发炎。扩散和软骨破坏。尽管抗炎治疗，滑膜成纤维细胞活化仍持续的原因尚不清楚。一种可能是滑膜被逐渐成熟的具有改变特性的未成熟的间充质和骨髓细胞所填充。探索这个假设。我们研究了无翅（wnt）和卷曲的（fz）家族的各种胚胎生长因子在RA滑膜组织中的表达，这些因子与骨髓祖细胞和肢体芽间充质细胞命运的确定有关。逆转录酶-PCR分析揭示了RA滑膜组织中5种wnt（wntt。5a，10b，1 f。和13）和3种fz（fz2，i和7）亚型的表达。骨关节炎滑膜组织表达的wn58和fz5少得多。与一组正常的成人组织相比，Northern印迹证实了wnt5a和fz5在RA滑膜组织中的过表达。与正常滑膜成纤维细胞相比，培养的RA成纤维样滑膜细胞表达更高水平的IL-6，IL-8。和LL-1S。用wnt5a表达载体转染正常成纤维细胞可重现这种细胞因子表达模式，并刺激IL-1 S分泌。这些结果表明，RA成纤维细胞的异常表型特性可能部分归因于它们被具有不成熟骨髓和间充质细胞特征的原始成纤维细胞样滑膜细胞所替代。由RA滑膜中的wn t5a / fzS配体-受体对引发的信号通路的清晰描述可能会产生治疗干预的新靶标。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号