血管生成素样蛋白4是关节炎中一种潜在的血管生成介质。

Angiopoietin-like-4 is a potential angiogenic mediator in arthritis.

作者信息

Hermann L M, Pinkerton M, Jennings K, Yang L, Grom A, Sowders D, Kersten S, Witte D P, Hirsch R, Thornton S

机构信息

William S. Rowe Division of Rheumatology, Cincinnati Children's Hospital, 3333 Burnet Avenue, ML 4010, Cincinnati, OH 45229, USA.

出版信息

Clin Immunol. 2005 Apr;115(1):93-101. doi: 10.1016/j.clim.2004.12.002.

DOI:10.1016/j.clim.2004.12.002

PMID:15870027

Abstract

Our previous studies of gene expression profiling during collagen-induced arthritis (CIA) indicated that the putative angiogenic factor Angptl4 was one of the most highly expressed mRNAs early in disease. To investigate the potential involvement of Angptl4 in CIA pathogenesis, Angptl4 protein levels were assessed at early stages of disease and its cellular sources were determined. In addition, the functional effects of mouse Angptl4 on endothelial cells were assessed. Angptl4 protein levels were higher in arthritic joints as compared to normal joints. In situ hybridization localized Angptl4 mRNA to stromal fibroblast-like cells within the inflamed synovium. Temporal expression of Angptl4 mRNA during CIA was similar to that of key angiogenic factors, including structurally related angiopoietin 1. Recombinant mouse Angptl4 promoted endothelial cell survival and formation of tubule-like structures. These functional effects of Angptl4, combined with very high expression at early stages of CIA, suggest a role for Angptl4 in angiogenesis in arthritis.

摘要

我们之前对胶原诱导性关节炎（CIA）期间基因表达谱的研究表明，假定的血管生成因子血管生成素样蛋白4（Angptl4）是疾病早期表达最高的mRNA之一。为了研究Angptl4在CIA发病机制中的潜在作用，我们在疾病早期评估了Angptl4蛋白水平，并确定了其细胞来源。此外，还评估了小鼠Angptl4对内皮细胞的功能影响。与正常关节相比，关节炎关节中的Angptl4蛋白水平更高。原位杂交将Angptl4 mRNA定位于炎症滑膜内的基质成纤维样细胞。CIA期间Angptl4 mRNA的时间表达与关键血管生成因子相似，包括结构相关的血管生成素1。重组小鼠Angptl4促进内皮细胞存活和管状结构形成。Angptl4的这些功能作用，加上其在CIA早期的高表达，提示Angptl4在关节炎血管生成中发挥作用。