Vascular endothelial growth factor C attenuates joint damage in chronic inflammatory arthritis by accelerating local lymphatic drainage in mice.
Vascular endothelial growth factor C attenuates joint damage in chronic inflammatory arthritis by accelerating local lymphatic drainage in mice.
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DOI：
10.1002/art.30421
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发表时间：
2011-08
影响因子：
--
通讯作者：
Xing, Lianping
中科院分区：
文献类型：
--
作者：
Zhou, Quan;Guo, Ruolin;Wood, Ronald;Boyce, Brendan F.;Liang, Qianqian;Wang, Yong-Jun;Schwarz, Edward M.;Xing, Lianping
目的：探讨关节内注射血管内皮生长因子C(VEGF-C)腺相关病毒(AAV)促进关节淋巴管生成对慢性炎症性关节炎的治疗作用。采用肿瘤坏死因子转基因(TNF-TG)小鼠作为慢性炎症性关节炎模型。将人血管内皮生长因子-C克隆到AAV表达载体中，构建成AAV-VEGF-C。将AAV-VEGF-C或对照AAV-Luc注射到肿瘤坏死因子-Tg小鼠的关节内。在注射后的4个月内，使用MRI和淋巴成像来评估滑膜体积和从关节组织到局部引流淋巴结的淋巴流量的变化。组织学检查关节炎症、骨质侵蚀和软骨丢失情况。免疫组织化学方法检测淋巴管形成情况。与AAV-Luc病毒相比，关节内注射AAV-VEGF-C病毒显著减轻了关节切片中滑膜体积的增加和淋巴管数量的增加。伴随而来的是炎症面积减少、骨质侵蚀、软骨丢失和破骨细胞数量。从关节到局部引流淋巴结的淋巴流动在肿瘤坏死因子-甘油三酯小鼠中比野生型小鼠慢，经AAV-VEGF-C治疗后显著改善。关节内注射AAV-VEGF-C可增加淋巴管生成，改善炎症关节的淋巴引流，从而减轻关节组织损伤。因此，局部应用淋巴生长因子改善关节淋巴功能是治疗慢性炎症性关节炎的新途径。
To investigate if enhancement of joint lymphangiogenesis by injecting VEGF-C adeno-associated virus (AAV) into joints has therapeutic efficacy in chronic inflammatory arthritis in mice. TNF transgenic (TNF-Tg) mice were used as a model of chronic inflammatory arthritis. Human VEGF-C was cloned into an AAV expression vector to generate AAV-VEGF-C. AAV-VEGF-C or control AAV-Luc was injected into joints of TNF-Tg mice. MRI and lymphatic imaging were used during the 4-months following injection to assess changes in synovial volume and lymph flow from joint tissues to local draining lymph nodes. Joint inflammation, bone erosion and cartilage loss were examined by histologic analyses. Lymphatic vessel formation was assessed using immunohistochemistry. Intra-articular administration of AAV-VEGF-C virus significantly attenuated the increase in synovial volume and increased lymphatic vessel number in joint sections compared to AAV-Luc virus during the 4-month-period. This accompanied by reduced inflammation area, bone erosion, cartilage loss, and osteoclast numbers. Lymph flow from joints to local draining lymph nodes was slower in TNF-Tg mice than in wild-type littermates and was significantly improved with AAV-VEGF-C treatment. Intra-articular injection of AAV-VEGF-C increased lymphangiogenesis and improved lymphatic drainage from inflamed joints, resulting in attenuation of joint tissue damage. Thus, improvement of joint lymphatic function by local administration of lymphatic growth factors represents a new therapeutic approach for chronic inflammatory arthritis.
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影响因子：
37.8
作者：
Nykanen, Antti I.;Sandelin, Henrik;Lemstrom, Karl B.
通讯作者：
Lemstrom, Karl B.
影响因子：
--
作者：
Hayer, Silvia;Redlich, Kurt;Schett, Georg
通讯作者：
Schett, Georg
影响因子：
6.5
作者：
Kajiya, Kentaro;Sawane, Mika;Detmar, Michael
通讯作者：
Detmar, Michael
在慢性炎性关节炎的小鼠模型中，通过血管内皮生长因子受体3封锁抑制淋巴管生成和淋巴引流会增加炎症的严重程度。
影响因子：
--
作者：
Guo, Ruolin;Zhou, Quan;Proulx, Steven T.;Wood, Ronald;Ji, Rui-Cheng;Ritchlin, Christopher T.;Pytowski, Bronislaw;Zhu, Zhenping;Wang, Yong-Jun;Schwarz, Edward M.;Xing, Lianping
通讯作者：
Xing, Lianping
DOI：
10.1084/jem.20100559
发表时间：
2010-09-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Huggenberger R;Ullmann S;Proulx ST;Pytowski B;Alitalo K;Detmar M
通讯作者：
Detmar M