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健康与疾病状态下的内皮细胞转胞吞作用。

Endothelial transcytosis in health and disease.

作者信息

Simionescu Maya, Popov Doina, Sima Anca

机构信息

Institute of Cellular Biology and Pathology, Nicolae Simionescu, Bucharest, Romania.

出版信息

Cell Tissue Res. 2009 Jan;335(1):27-40. doi: 10.1007/s00441-008-0688-3. Epub 2008 Oct 3.

DOI:10.1007/s00441-008-0688-3
PMID:18836747
Abstract

The visionaries predicted the existence of transcytosis in endothelial cells; the cell biologists deciphered its mechanisms and (in part) the molecules involved in the process; the cell pathologists unravelled the presence of defective transcytosis in some diseases. The optimistic perspective is that transcytosis, in general, and receptor-mediated transcytosis, in particular, will be greatly exploited in order to target drugs and genes to exclusive sites in and on endothelial cells (EC) or underlying cells. The current recognition that plasmalemmal vesicles (caveolae) are the vehicles involved in EC transcytosis has moved through various phases from initial considerations of caveolae as unmovable sessile non-functional plasmalemma invaginations to the present identification of a multitude of molecules and a crowd of functions associated with these ubiquitous structures of endothelial and epithelial cells. Further understanding of the molecular machinery that precisely guides caveolae through the cells so as to reach the target membrane (fission, docking, and fusion), to avoid lysosomes, or on the contrary, to reach the lysosomes, and discharge the cargo molecules will assist in the design of pathways that, by manipulating the physiological route of caveolae, will carry molecules of choice (drugs, genes) at controlled concentrations to precise destinations.

摘要

有远见者预言了内皮细胞转胞吞作用的存在;细胞生物学家阐明了其机制以及(部分)该过程中涉及的分子;细胞病理学家揭示了某些疾病中存在有缺陷的转胞吞作用。乐观的看法是,一般而言的转胞吞作用,尤其是受体介导的转胞吞作用,将被大力利用,以便将药物和基因靶向到内皮细胞(EC)及其下方细胞内和表面的特定部位。目前已认识到质膜小泡(小窝)是参与内皮细胞转胞吞作用的载体,这一认识经历了多个阶段,从最初将小窝视为不可移动的无功能质膜内陷,到如今识别出众多与内皮细胞和上皮细胞这些普遍存在的结构相关的分子及大量功能。进一步了解精确引导小窝穿过细胞以到达靶膜(分裂、对接和融合)、避开溶酶体,或者相反,到达溶酶体并释放货物分子的分子机制,将有助于设计相关途径,即通过操纵小窝的生理路径,将选定的分子(药物、基因)以可控浓度输送到精确的目的地。

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