Lymphatic endothelial cells, lymphangiogenesis, and extracellular matrix
Lymphatic endothelial cells, lymphangiogenesis, and extracellular matrix
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DOI：
10.1089/lrb.2006.4.83
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发表时间：
2006-01-01
影响因子：
1.4
通讯作者：
Ji, Rui-Cheng
中科院分区：
文献类型：
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作者：
Ji, Rui-Cheng
淋巴相关疾病(如伤口愈合、淋巴水肿和肿瘤转移)中淋巴管生成的分子调控研究重新引起了人们对淋巴管内皮细胞(LECs)和细胞外基质(ECM)微环境之间内在关系的关注。ECM分子和重塑事件在调节淋巴管生成中起关键作用，而与“功能性”相关的分子，特别是透明质酸、整合素、reelin、IL-7和基质金属蛋白酶，为LEC的生长、迁移、管形成和存活提供了最基本和最关键的先决条件，尽管淋巴管生成在胚胎和病理过程中直接或/和间接受VEGF-C/-DNEGFR3-Prox-1-、Syk/SLP76-、podoplan in/Ang-2/NRP-2-、FOXC2-等信号通路控制。关于初始淋巴管分化的新知识应该有助于提高对各种细胞因子、趋化因子和其他因素的理解。通过使用新的分子标记(如LYVE-1)进行淋巴共定位和组织化学染色，以及随后的铁蛋白或某些示踪剂注射技术，将揭示新形成和先前存在的淋巴管的功能和结构特征。对ECM和LEC分子在重要生理和病理事件中的多种功能的日益认识，可能有助于识别淋巴循环组织中的关键变化，最终有助于寻找合理的治疗方法来预防淋巴相关疾病。
Exciting studies involving the molecular regulation of lymphangiogenesis in lymphatic-associated disorders (e.g., wound healing, lymphedema and tumor metastasis) have focused renewed attention on the intrinsic relationship between lymphatic endothelial cells (LECs) and extracellular matrix (ECM) microenvironment. ECM molecules and remodeling events play a key role in regulating lymphangiogenesis, and the "functionality"-relating molecules, especially hyaluronan, integrins, reelin, IL-7, and matrix metalloproteinases, provide the most fundamental and critical prerequisite for LEC growth, migration, tube formation, and survival, although lymphangiogenesis is directly or/and indirectly controlled by VEGF-C/-DNEGFR3- Prox-1-, Syk/SLP76-, podoplanin/Ang-2/Nrp-2-, FOXC2-, and other signaling pathways in embryonic and pathological processes. New knowledge regarding the differentiation of initial lymphatics should enable improvements in understanding of a variety of cytokines, chemokines, and other factors. The lymphatic colocalization with histochemical staining by using the novel molecular markers (e.g., LYVE-1), along with subsequent injection technique with ferritin or some tracer, will reveal functional and structural features of newly formed and preexisting lymphatics. Growing recognition of the multiple functions of ECM and LEC molecules for important physiological and pathological events may be helpful in identifying the crucial changes in tissues subjected to lymph circulation and ultimately in the search for rational therapeutic approaches to prevent lymphatic-associated disorders.