Trimarchi Hernán, Ortiz Alberto, Sánchez-Niño Maria Dolores
Nephrology Service, Hospital Británico de Buenos Aires, 1280 Buenos Aires, Argentina.
IIS-Fundación Jimenez Díaz, School of Medicine, UAM, 28040 Madrid, Spain.
J Clin Med. 2020 Nov 13;9(11):3659. doi: 10.3390/jcm9113659.
Podocyturia in Fabry nephropathy leads to glomerulosclerosis and kidney disease progression. Integrins are involved in podocyte attachment to the glomerular basement membrane. We hypothesized that in Fabry nephropathy, lyso-Gb3 could modulate αvβ3 expression in podocytes. Together with UPAR, the αvβ3 integrin is a key mechanism involved in podocyte detachment and podocyturia.
In cultured human podocytes stimulated with lyso-Gb3, the mRNA expression of the and genes encoding integrins αv and β3, respectively, was analyzed by RT-qPCR.
In cultured human podocytes, lyso-Gb3 at concentrations encountered in the serum of Fabry patients increased and mRNA levels within 3 to 6 h. This pattern of gene expression is similar to that previously observed for gene expression but is in contrast to the delayed (24 h) upregulation of other markers of podocyte stress and mediators of injury, such as CD80, TGFβ1, CD74, Notch1, and HES.
Human podocyte stress in response to glycolipid overload in Fabry nephropathy, exemplified by lyso-Gb3, is characterized by an early increase in the expression of components of the αvβ3/UPAR system, which contrasts with the delayed rise in the expression of other mediators of podocyte injury. This suggests that the αvβ3/UPAR system may be a therapeutic target in Fabry nephropathy.
法布里肾病中的足细胞尿可导致肾小球硬化和肾脏疾病进展。整合素参与足细胞与肾小球基底膜的附着。我们推测，在法布里肾病中，溶血型Gb3可调节足细胞中αvβ3的表达。αvβ3整合素与尿激酶型纤溶酶原激活物受体（UPAR）一起，是参与足细胞脱离和足细胞尿的关键机制。
在用溶血型Gb3刺激的培养人足细胞中，通过逆转录定量聚合酶链反应（RT-qPCR）分析分别编码整合素αv和β3的 和 基因的mRNA表达。
在培养的人足细胞中，法布里病患者血清中存在的浓度的溶血型Gb3在3至6小时内增加了 和 的mRNA水平。这种基因表达模式与先前观察到的 基因表达模式相似，但与足细胞应激和损伤介质（如CD80、转化生长因子β1、CD74、Notch1和HES）的延迟（24小时）上调形成对比。
以溶血型Gb3为例，法布里肾病中糖脂过载引起的人足细胞应激的特征是αvβ3/UPAR系统成分的表达早期增加，这与足细胞损伤的其他介质表达的延迟增加形成对比。这表明αvβ3/UPAR系统可能是法布里肾病的治疗靶点。
