Angiopoietin-like 4 based therapeutics for proteinuria and kidney disease.
Angiopoietin-like 4 based therapeutics for proteinuria and kidney disease.
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类似于血管蛋白的4种基于4的蛋白尿和肾脏疾病的疗法。
DOI：
10.3389/fphar.2014.00023
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发表时间：
2014
影响因子：
5.6
通讯作者：
Marshall CB
中科院分区：
文献类型：
--
作者：
Chugh SS;Macé C;Clement LC;Del Nogal Avila M;Marshall CB
目前用于治疗蛋白尿肾病的药物是从其他医学分支借来的，而且只是部分有效。两种不同形式的分泌糖蛋白血管生成素样4 （Angptl4）在人类和实验性肾小球疾病中发挥核心机制作用的发现开辟了新的治疗途径。足细胞分泌的Angptl4低羟化形式（缺乏唾液酸残基）的局部上调诱导了人类微小变化疾病的主要形态学和临床表现，并且也越来越多地被认为是实验性糖尿病肾病中蛋白尿的重要因素。口服低剂量n -乙酰- d -甘露糖胺（天然存在的唾液酸前体）可改善体内Angptl4的唾液化，并减少40%以上的蛋白尿。相比之下，唾液化循环形式的Angptl4，主要由骨骼肌、心脏和脂肪组织分泌，在所有主要的原发性肾小球疾病中，减少蛋白尿，同时也引起高甘油三酯血症。静脉给药重组人Angptl4以避免高甘油三酯血症和卵裂，在单次低剂量后2周内可显著减少蛋白尿65%。这两种干预措施在机制上是相关的，利用自然发生的途径，代表了与肾小球疾病相关的慢性肾脏疾病的新一代治疗药物。
Current drugs used to treat proteinuric disorders of the kidney have been borrowed from other branches of medicine, and are only partially effective. The discovery of a central, mechanistic role played by two different forms of the secreted glycoprotein angiopoietin-like 4 (Angptl4) in human and experimental glomerular disease has opened new treatment avenues. Localized upregulation of a hyposialylated form (lacks sialic acid residues) of Angptl4 secreted by podocytes induces the cardinal morphological and clinical manifestations of human minimal change disease, and is also being increasingly recognized as a significant contributor toward proteinuria in experimental diabetic nephropathy. Oral treatment with low doses of N-acetyl-D-mannosamine, a naturally occurring precursor of sialic acid, improves sialylation of Angptl4 in vivo, and reduces proteinuria by over 40%. By contrast, a sialylated circulating form of Angptl4, mostly secreted from skeletal muscle, heart and adipose tissue in all major primary glomerular diseases, reduces proteinuria while also causing hypertriglyceridemia. Intravenous administration of recombinant human Angptl4 mutated to avoid hypertriglyceridemia and cleavage has remarkable efficacy in reducing proteinuria by as much as 65% for 2 weeks after a single low dose. Both interventions are mechanistically relevant, utilize naturally occurring pathways, and represent new generation therapeutic agents for chronic kidney disease related to glomerular disorders.
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影响因子：
19.6
作者：
GHIGGERI, GM;GINEVRI, F;GUSMANO, R
通讯作者：
GUSMANO, R
影响因子：
5.2
作者：
KOSKIMIES, O;VILSKA, J;HALLMAN, N
通讯作者：
HALLMAN, N
影响因子：
4.8
作者：
Mandard, S;Zandbergen, F;Kersten, S
通讯作者：
Kersten, S
循环血管生成素样4将蛋白尿与肾病综合征中的高甘油三酸血症联系起来。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
6.5
作者：
Yoshida, K;Shimizugawa, T;Furukawa, H
通讯作者：
Furukawa, H