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Glomerüler Endotel Hastalıklarının Tedavisinde Yeni Ufuklar

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New Insight into Treatment of Diseases of Glomerular Endothelium

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Sayfa Aralığı:: 
220-226

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Abstract (Original Language): 
Böbrekten plazmanın ultrafi ltrasyonu, glomerüler endotelyal hücreler, glomerüler bazal membrane ve podositlerden oluşan glomerüler kapiller duvar üzerinden gerçekleşir. Glomerüler endotel hücreleri, sitoplazmaları çok sayıda fenestralarla kaplanmış ve glomerüler fi ltrasyon bariyerinin ileri düzeyde özelleşmiş bir parçasıdır. Bu fi ltrasyon fonksiyonunda fenestraların rolü çok iyi anlaşılamamıştır. Öte yandan glomerüler endotelin bir parçası olan glomerüler endotelyal glikokaliksin varlığı makromoleküllerin bariyerine anlamlı ölçüde katkı sağlamaktadır. Vasküler endotelyal büyüme faktörü (VEGF) oldukça önemli bir büyüme faktörüdür ve böbrekteki anjiyogenik sitokinleri düzenler. Yapılan çalışmalarda; in vivo modellerde VEGF’ün aşırı ekspresyonunun, in vitro sistemlerde de farmakolojik ajanların dışarıdan verilmesinin fenestraların oluşumları ile yakın birlikteliği gösterilmiştir. Glomerüler endotel hücrelerin, glomerüler fi zyoloji ve patolojisi ile olan beraberliklerinin büyük ölçüde anlaşılması, doğal olarak tedavide muhtemel gelişmelerin olabilirliği sorularını artırmıştır. Örneğin, şiddetli preeklampside böbrek yetmezliği gelişimini önleyeceğinden fenestra formasyonunun artırılması arzu edilir ve yine aynı yolla diyabetik nefropati gibi pek çok tabloda glomerüler fi ltrasyon hızının artırılması sağlanabilir. Yakın gelecekte, glomerüler fi ltrasyon bariyerindeki patolojinin daha iyi anlaşılması için geliştirilen deneysel metodların kullanımı ile birlikte proteinürik böbrek hastalıklarının tedavisinde hedefe yönelik yeni moleküllerin bulunması da söz konusu olacaktır.
Abstract (2. Language): 
The capillary wall of the glomerulus, which is composed of glomerular endothelial cells (GECs), the glomerular basement membrane (GBM), and podocytes, is responsible for the ultrafi ltration of plasma in the kidney. The function of the fenestrated endothelium in fi ltration is poorly understood. On the other hand, the presence of a signifi cant glomerular endothelial glycocalyx implies that the glomerular endothelium signifi cantly contributes to the barrier to macromolecules. Vascular endothelial growth factor (VEGF) is the most important and tightly regulated angiogenic cytokine in the kidney. Studies of fenestration formation have relied on overexpression of VEGF in in vivo models or on in vitro systems where VEGF or pharmacological agents are added exogenously. A greater understanding of the glomerular endothelial cells relevance of in glomerular physiology and pathology naturally raises the question of whether it will be possible to manipulate them therapeutically. For example, promotion of fenestration formation would be desirable in severe preeclampsia to avoid renal failure and may increase GFR in a number of other conditions, including diabetic nephropathy. In the near future, the use of experimental methods will further expand understanding of the pathology of the glomerular fi ltration barrier, and perhaps reveal novel target molecules for the therapy of proteinuric kidney diseases.

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DOI: 
10.5262/tndt.2011.1003.03

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