The importance of podocyte adhesion for a healthy glomerulus.
The importance of podocyte adhesion for a healthy glomerulus.
复制标题
足细胞粘附对健康肾小球的重要性。
DOI：
10.3389/fendo.2014.00160
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发表时间：
2014
影响因子：
5.2
通讯作者：
Humphries MJ
中科院分区：
文献类型：
--
作者：
Lennon R;Randles MJ;Humphries MJ
足细胞是覆盖在肾小球毛细血管外表面的特化上皮细胞。独特的细胞连接，被称为狭缝隔膜，它具有nephrin和Neph家族蛋白，以及粘附、紧密和间隙连接的成分，连接相邻的足细胞足突。影响狭缝横膈膜的单基因疾病导致人类肾病综合征，其特征是毛细血管壁蛋白质的大量损失。除了特化的细胞连接外，相互连接的足细胞也粘附在毛细血管壁的肾小球基底膜上。GBM是一个由分泌的细胞外基质（ECM）成分组成的致密网络，除了其他结构蛋白和ECM调节因子（如蛋白酶和生长因子）外，还含有胶原IV和层粘连蛋白的组织限制性同型体。GBM的特殊生态位为内皮细胞和足细胞提供了支持其独特功能的支架，GBM成分的人类基因突变可导致肾衰竭，因此强调了肾小球中细胞-基质相互作用的重要性。细胞通过粘附受体粘附到ECM上，包括整合素、syndecans和dysstrodglycan，特别是整合素异二聚体α3β1是维持屏障完整性所必需的。因此，肾小球滤过的复杂功能依赖于足细胞在细胞连接处和与ECM界面的粘附。在健康情况下，足细胞协调来自细胞连接和细胞-基质相互作用的信号，以响应环境信号来调节滤过，随着我们对肾小球细胞粘附控制机制的理解的发展，对疾病影响的了解将会改善。最终目标将是开发靶向治疗，以预防或修复滤过屏障的缺陷，并恢复肾小球功能。
Podocytes are specialized epithelial cells that cover the outer surfaces of glomerular capillaries. Unique cell junctions, known as slit diaphragms, which feature nephrin and Neph family proteins in addition to components of adherens, tight, and gap junctions, connect adjacent podocyte foot processes. Single gene disorders affecting the slit diaphragm result in nephrotic syndrome in humans, characterized by massive loss of protein across the capillary wall. In addition to specialized cell junctions, interconnecting podocytes also adhere to the glomerular basement membrane (GBM) of the capillary wall. The GBM is a dense network of secreted, extracellular matrix (ECM) components and contains tissue-restricted isoforms of collagen IV and laminin in addition to other structural proteins and ECM regulators such as proteases and growth factors. The specialized niche of the GBM provides a scaffold for endothelial cells and podocytes to support their unique functions and human genetic mutations in GBM components lead to renal failure, thus highlighting the importance of cell–matrix interactions in the glomerulus. Cells adhere to ECM via adhesion receptors, including integrins, syndecans, and dystroglycan and in particular the integrin heterodimer α3β1 is required to maintain barrier integrity. Therefore, the sophisticated function of glomerular filtration relies on podocyte adhesion both at cell junctions and at the interface with the ECM. In health, the podocyte coordinates signals from cell junctions and cell–matrix interactions, in response to environmental cues in order to regulate filtration and as our understanding of mechanisms that control cell adhesion in the glomerulus develops, then insight into the effects of disease will improve. The ultimate goal will be to develop targeted therapies to prevent or repair defects in the filtration barrier and to restore glomerular function.
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影响因子：
6
作者：
Baleato, Rosa M.;Guthrie, Petrina L.;Roselli, Severine
通讯作者：
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影响因子：
3.3
作者：
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影响因子：
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DOI：
10.1073/pnas.0811415106
发表时间：
2008-12-30
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
19.6
作者：
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通讯作者：
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