Glomerular endothelial cell fenestrations: an integral component of the glomerular filtration barrier.
Glomerular endothelial cell fenestrations: an integral component of the glomerular filtration barrier.
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DOI：
10.1152/ajprenal.90601.2008
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发表时间：
2009-05
期刊：
影响因子：
--
通讯作者：
Braet F
中科院分区：
文献类型：
--
作者：
Satchell SC;Braet F
肾小球内皮细胞（GEnC）窗孔类似于足细胞滤过狭缝，但其对肾小球滤过屏障的重要作用尚未得到相应的重视。GEnC窗孔是跨胞浆孔，专门用于其作为穿过肾小球毛细血管壁过滤的先决条件的独特作用。肾小球滤过率取决于开窗的面积分数，并且通过它们所包含的糖萼，GEnC开窗在限制蛋白质通过方面是重要的。因此，GEnC开窗的失调可能与肾衰竭和蛋白尿相关，并且GEnC开窗的病理生理学重要性在诸如先兆子痫的病症中得到了很好的表征。最近的证据表明，在肾小球损伤和常见但严重的疾病（包括糖尿病肾病）的修复中具有更广泛的意义。内皮细胞开窗的研究是具有挑战性的，因为有限的可用性合适的体外模型和电子显微镜成像这些亚100纳米结构的要求。然而，从啮齿类动物的肾小球发育到人类GEnC的体外研究，大量证据表明血管内皮生长因子（VEGF）是开窗的关键诱导剂。在系统性内皮开窗中，VEGF诱导开窗的细胞内途径包括窗隔蛋白质膜囊泡相关蛋白-1（PV-1）的关键作用。PV-1在GEnC中的作用尚不清楚，尤其是因为对GEnC窗隔的存在争议。在这篇文章中，GEnC开窗的结构-功能关系将进行深入评估，它们在健康和疾病中的作用进行了探讨，并对这些特殊结构的未来研究和治疗意义进行了展望。
Glomerular endothelial cell (GEnC) fenestrations are analogous to podocyte filtration slits, but their important contribution to the glomerular filtration barrier has not received corresponding attention. GEnC fenestrations are transcytoplasmic holes, specialized for their unique role as a prerequisite for filtration across the glomerular capillary wall. Glomerular filtration rate is dependent on the fractional area of the fenestrations and, through the glycocalyx they contain, GEnC fenestrations are important in restriction of protein passage. Hence, dysregulation of GEnC fenestrations may be associated with both renal failure and proteinuria, and the pathophysiological importance of GEnC fenestrations is well characterized in conditions such as preeclampsia. Recent evidence suggests a wider significance in repair of glomerular injury and in common, yet serious, conditions, including diabetic nephropathy. Study of endothelial cell fenestrations is challenging because of limited availability of suitable in vitro models and by the requirement for electron microscopy to image these sub-100-nm structures. However, extensive evidence, from glomerular development in rodents to in vitro studies in human GEnC, points to vascular endothelial growth factor (VEGF) as a key inducer of fenestrations. In systemic endothelial fenestrations, the intracellular pathways through which VEGF acts to induce fenestrations include a key role for the fenestral diaphragm protein plasmalemmal vesicle-associated protein-1 (PV-1). The role of PV-1 in GEnC is less clear, not least because of controversy over existence of GEnC fenestral diaphragms. In this article, the structure-function relationships of GEnC fenestrations will be evaluated in depth, their role in health and disease explored, and the outlook for future study and therapeutic implications of these peculiar structures will be approached.
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影响因子：
13.5
作者：
BRAET, F;DEZANGER, R;WISSE, E
通讯作者：
WISSE, E
影响因子：
3.1
作者：
BANKSTON, PW;MILICI, AJ
通讯作者：
MILICI, AJ
影响因子：
5.5
作者：
Chen, J;Braet, F;Goligorsky, MS
通讯作者：
Goligorsky, MS
DOI：
10.1073/pnas.101564798
发表时间：
2001-05-22
影响因子：
11.1
作者：
Cao, RH;Brakenhielm, E;Cao, YH
通讯作者：
Cao, YH
影响因子：
--
作者：
Braet, F;Spector, I;Wisse, E
通讯作者：
Wisse, E