Junctional adhesion molecule-A is abnormally expressed in diffuse cutaneous systemic sclerosis skin and mediates myeloid cell adhesion
Junctional adhesion molecule-A is abnormally expressed in diffuse cutaneous systemic sclerosis skin and mediates myeloid cell adhesion
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DOI：
10.1136/ard.2008.102624
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发表时间：
2010-01-01
影响因子：
27.4
通讯作者：
Koch, A. E.
中科院分区：
文献类型：
--
作者：
Hou, Y.;Rabquer, B. J.;Koch, A. E.
目的：目的：探讨连接粘附分子A（JAM-A）在系统性硬化症（SSc）发病中的作用。为了确定SSc真皮成纤维细胞和SSc皮肤中JAM-A的表达，进行细胞表面ELISA和免疫组织学。设计ELISA以测定血清中可溶性JAM-A（sJAM-A）的量。结果：与正常志愿者相比，SSc皮肤颗粒层和真皮内皮细胞（ECs）中JAM-A的表达明显降低。然而，与正常志愿者相比，SSc患者血清中sJAM-A升高。相反，与正常真皮成纤维细胞相比，SSc表面的JAM-A增加。JAM-A占U937与SSc真皮成纤维细胞结合的显著部分。此外，JAM-A有助于U937粘附到远端和近端SSc skin.Conclusions：JAM-A表达失调SSc皮肤。SSc EC上JAM-A表达的降低可能导致对促血管生成碱性成纤维细胞生长因子的反应降低。SSc成纤维细胞上增加的JAM-A表达可用于保留髓样细胞，髓样细胞进而分泌血管生成因子。
Objective: To investigate the role of junctional adhesion molecule-A (JAM-A) in the pathogenesis of systemic sclerosis (SSc).Methods: Biopsy specimens from proximal and distal arm skin and serum were obtained from patients with SSc and normal volunteers. To determine the expression of JAM-A on SSc dermal fibroblasts and in SSc skin, cell surface ELISAs and immunohistology were performed. An ELISA was designed to determine the amount of soluble JAM-A (sJAM-A) in serum. Myeloid U937 cell-SSc dermal fibroblast and skin adhesion assays were performed to determine the role of JAM-A in myeloid cell adhesion.Results: The stratum granulosum and dermal endothelial cells (ECs) from distal arm SSc skin exhibited significantly decreased expression of JAM-A in comparison with normal volunteers. However, sJAM-A was increased in the serum of patients with SSc compared with normal volunteers. Conversely, JAM-A was increased on the surface of SSc compared with normal dermal fibroblasts. JAM-A accounted for a significant portion of U937 binding to SSc dermal fibroblasts. In addition, JAM-A contributed to U937 adhesion to both distal and proximal SSc skin.Conclusions: JAM-A expression is dysregulated in SSc skin. Decreased expression of JAM-A on SSc ECs may result in a reduced response to proangiogenic basic fibroblast growth factor. Increased JAM-A expression on SSc fibroblasts may serve to retain myeloid cells, which in turn secrete angiogenic factors.