Renal Glomerular Expression of WT-1, TGF-β, VEGF, and ET-1 Immunostains in Murine Models of Focal and Segmental Glomerulosclerosis.

IF 1.3 4区 医学 Q3 ANATOMY & MORPHOLOGY Applied Immunohistochemistry & Molecular Morphology Pub Date : 2023-09-01 Epub Date: 2023-08-03 DOI:10.1097/PAI.0000000000001146
Sufia Husain
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Abstract

Primary focal segmental glomerulosclerosis (FSGS) is a type of chronic renal disease that commonly progresses to renal failure as the treatments are not particularly effective. Glomerular podocyte injury and loss are pivotal to the pathogenesis of FSGS. This study aims to explore the glomerular immunohistochemistry stain expression of Wilms tumor-1 (WT-1) (podocyte-specific protein), transforming growth factor beta (TGF-β) (cytokine protein), vascular endothelial growth factor (VEGF) (angiogenic protein), and endothelin-1 (ET-1) (profibrotic growth factor), in rats with adriamycin nephropathy, which represents the murine model of human FSGS. By the end of 8 and 12 weeks, the kidneys of adriamycin-treated rats and control rats were harvested and the histomorphology was studied. Both 8- and 12-week test groups developed proteinuria, and hypoalbuminemia and showed FSGS on hematoxylin and eosin-stained slides. The renal tissue samples were also treated with immunostains for WT-1, TGF-β, VEGF, and ET-1. The glomeruli in all the FSGS kidneys showed loss of WT-1 expression with a concomitant notable increased expression of TGF-β, VEGF, and ET-1 immunostains. These results demonstrate that as FSGS evolves, the WT-1-expressing podocytes are lost and it correlates inversely with the overexpression of TGF-β, VEGF, and ET-1, suggesting that during the pathogenesis of FSGS, podocyte damage triggers the activation of these proteins. The findings in the current study echo the theory hypothesized in world literature that TGF-β, VEGF, and ET-1 play an integral part in the evolution of FSGS. More research is needed to further detail the pathogenic role of these proteins as it may open routes to more targeted and effective treatment modalities.

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肾肾小球WT-1、TGF-β、VEGF和ET-1在局灶性和节段性肾小球硬化症小鼠模型中的表达。
原发性局灶节段性肾小球硬化症(FSGS)是一种慢性肾脏疾病,由于治疗效果不佳,通常会发展为肾衰竭。肾小球足细胞损伤和丢失是FSGS发病机制的关键。本研究旨在探讨肾母细胞瘤1(WT-1)(足细胞特异性蛋白)、转化生长因子β(TGF-β)(细胞因子蛋白)、血管内皮生长因子(VEGF)(血管生成蛋白)和内皮素-1(ET-1)(促纤维化生长因子)在阿霉素肾病大鼠肾小球中的免疫组织化学染色表达,这是人类FSGS的小鼠模型。在8周和12周结束时,收获阿霉素处理的大鼠和对照大鼠的肾脏,并研究其组织形态学。8周和12周的试验组均出现蛋白尿和低蛋白血症,苏木精和伊红染色的载玻片显示FSGS。肾组织样本也用WT-1、TGF-β、VEGF和ET-1的免疫染色处理。所有FSGS肾脏的肾小球显示WT-1表达缺失,同时TGF-β、VEGF和ET-1免疫染色的表达显著增加。这些结果表明,随着FSGS的进化,表达WT-1的足细胞丢失,并且与TGF-β、VEGF和ET-1的过度表达呈负相关,这表明在FSGS的发病机制中,足细胞损伤触发了这些蛋白质的激活。目前的研究结果与世界文献中假设的理论相呼应,即TGF-β、VEGF和ET-1在FSGS的进化中起着不可或缺的作用。需要更多的研究来进一步详细说明这些蛋白质的致病作用,因为它可能为更具针对性和有效的治疗模式开辟途径。
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来源期刊
Applied Immunohistochemistry & Molecular Morphology
Applied Immunohistochemistry & Molecular Morphology ANATOMY & MORPHOLOGY-MEDICAL LABORATORY TECHNOLOGY
CiteScore
3.20
自引率
0.00%
发文量
153
期刊介绍: ​Applied Immunohistochemistry & Molecular Morphology covers newly developed identification and detection technologies, and their applications in research and diagnosis for the applied immunohistochemist & molecular Morphologist. Official Journal of the International Society for Immunohistochemisty and Molecular Morphology​.
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