Smooth muscle-endothelial cell communication activates Reelin signaling and regulates lymphatic vessel formation.
Smooth muscle-endothelial cell communication activates Reelin signaling and regulates lymphatic vessel formation.
复制标题
平滑肌 - 内皮细胞通信激活reelin信号传导并调节淋巴管的形成。
DOI：
10.1083/jcb.201110132
复制
发表时间：
2012-06-11
期刊：
影响因子：
--
通讯作者：
Makinen T
中科院分区：
文献类型：
--
作者：
Lutter S;Xie S;Tatin F;Makinen T
Reelin信号通过收集淋巴管的两种细胞之间的交流而激活，并促进平滑肌细胞的募集，这是淋巴管形态发生和功能所必需的。活跃的淋巴运输依赖于收集淋巴管周围的平滑肌细胞（SMC）收缩，但对淋巴管壁组装和淋巴泵送的调节知之甚少。在这里，我们发现Reelin是一种细胞外基质糖蛋白，先前与中枢神经系统发育有关，是淋巴血管发育的重要调节因子。reelin缺陷小鼠表现为淋巴管收集异常，其特征是SMCs数量减少，淋巴管毛细血管标志物淋巴管内皮透明质酸受体1 （LYVE-1）表达异常，功能受损。此外，我们发现SMC募集到淋巴管刺激内皮源性Reelin的释放和蛋白水解加工。淋巴内皮细胞反过来通过上调单核细胞趋化蛋白1 （MCP1）的表达来响应Reelin，这表明Reelin介导的内皮因子表达调控在SMC募集上游的自分泌机制。这些结果揭示了一种机制，通过这种机制，Reelin信号被收集淋巴管的两种细胞类型（平滑肌细胞和内皮细胞）之间的交流激活，并突出了SMCs在淋巴管形态发生和功能中迄今未被认识到的重要功能。
Reelin signaling is activated by communication between the two cell types of the collecting lymphatic vessels and promotes smooth muscle cell recruitment, which is necessary for lymphatic vessel morphogenesis and function. Active lymph transport relies on smooth muscle cell (SMC) contractions around collecting lymphatic vessels, yet regulation of lymphatic vessel wall assembly and lymphatic pumping are poorly understood. Here, we identify Reelin, an extracellular matrix glycoprotein previously implicated in central nervous system development, as an important regulator of lymphatic vascular development. Reelin-deficient mice showed abnormal collecting lymphatic vessels, characterized by a reduced number of SMCs, abnormal expression of lymphatic capillary marker lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), and impaired function. Furthermore, we show that SMC recruitment to lymphatic vessels stimulated release and proteolytic processing of endothelium-derived Reelin. Lymphatic endothelial cells in turn responded to Reelin by up-regulating monocyte chemotactic protein 1 (MCP1) expression, which suggests an autocrine mechanism for Reelin-mediated control of endothelial factor expression upstream of SMC recruitment. These results uncover a mechanism by which Reelin signaling is activated by communication between the two cell types of the collecting lymphatic vessels—smooth muscle and endothelial cells—and highlight a hitherto unrecognized and important function for SMCs in lymphatic vessel morphogenesis and function.
登录
查看更多内容
影响因子：
11.8
作者：
Bazigou, Eleni;Xie, Sherry;Chen, Chun;Weston, Anne;Miura, Naoyuki;Sorokin, Lydia;Adams, Ralf;Muro, Andres F.;Sheppard, Dean;Makinen, Taija
通讯作者：
Makinen, Taija
影响因子：
16.2
作者：
Franco SJ;Martinez-Garay I;Gil-Sanz C;Harkins-Perry SR;Müller U
通讯作者：
Müller U
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
5.3
作者：
Jossin, Yves;Gui, Lanrun;Goffinet, Andre M.
通讯作者：
Goffinet, Andre M.
缺乏周细胞会导致内皮增生和异常血管形态发生。
影响因子：
7.8
作者：
Hellstrom, M;Gerhardt, H;Kalen, M;Li, X;Eriksson, U;Wolburg, H;Betsholtz, C
通讯作者：
Betsholtz, C