Satchell Simon C, Braet Filip
Academic Renal Unit, University of Bristol, Paul O'Gorman Lifeline Centre, Southmead Hospital, Bristol, BS10 5NB, United Kingdom.
Am J Physiol Renal Physiol. 2009 May;296(5):F947-56. doi: 10.1152/ajprenal.90601.2008. Epub 2009 Jan 7.
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.
肾小球内皮细胞（GEnC）窗孔类似于足细胞滤过裂隙，但其对肾小球滤过屏障的重要贡献尚未得到相应关注。GEnC窗孔是跨细胞质孔，因其作为肾小球毛细血管壁滤过前提条件的独特作用而具有特殊性。肾小球滤过率取决于窗孔的部分面积，并且通过其所含的糖萼，GEnC窗孔在限制蛋白质通过方面很重要。因此，GEnC窗孔失调可能与肾衰竭和蛋白尿均相关，并且GEnC窗孔的病理生理重要性在子痫前期等病症中已得到充分表征。最近的证据表明，其在肾小球损伤修复以及包括糖尿病肾病在内的常见但严重的病症中具有更广泛的意义。由于合适的体外模型有限，且需要电子显微镜对这些小于100纳米的结构进行成像，因此对内皮细胞窗孔的研究具有挑战性。然而，从啮齿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）是窗孔的关键诱导因子。在全身内皮窗孔中，VEGF诱导窗孔的细胞内途径包括窗孔隔膜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，尤其是因为关于GEnC窗孔隔膜是否存在存在争议。在本文中，将深入评估GEnC窗孔的结构-功能关系，探讨其在健康和疾病中的作用，并展望这些特殊结构的未来研究前景和治疗意义。
