Laboratory of Animal Models for Human Diseases, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Am J Physiol Renal Physiol. 2020 Jun 1;318(6):F1520-F1530. doi: 10.1152/ajprenal.00055.2020. Epub 2020 May 11.
Tensin2 (Tns2), an integrin-linked protein, is enriched in podocytes within the glomerulus. Previous studies have revealed that -deficient mice exhibit defects of the glomerular basement membrane (GBM) soon after birth in a strain-dependent manner. However, the mechanisms for the onset of defects caused by deficiency remains unidentified. Here, we aimed to determine the role of Tns2 using newborn deficient mice and murine primary podocytes. Ultrastructural analysis revealed that developing glomeruli during postnatal nephrogenesis exhibited abnormal GBM processing due to ectopic laminin-α accumulation followed by GBM thickening. In addition, analysis of primary podocytes revealed that deficiency led to impaired podocyte-GBM interaction and massive expression of laminin-α in podocytes. Our study suggests that weakened podocyte-GBM interaction due to deficiency causes increased mechanical stress on podocytes by continuous daily filtration after birth, resulting in stressed podocytes ectopically producing laminin-α, which interrupts GBM processing. We conclude that Tns2 plays important roles in the podocyte-GBM interaction and maintenance of the glomerular filtration barrier.
腱 2 蛋白（Tns2）是一种整合素连接蛋白，在肾小球中的足细胞中丰富表达。先前的研究表明，-缺陷小鼠在出生后不久就表现出肾小球基底膜（GBM）缺陷，这种缺陷具有菌株依赖性。然而，-缺乏引起缺陷的机制仍未确定。在这里，我们旨在使用新生-缺陷小鼠和鼠原代足细胞来确定 Tns2 的作用。超微结构分析显示，在出生后肾发生过程中发育中的肾小球由于层粘连蛋白-α的异位积累继而导致 GBM 增厚而表现出异常的 GBM 处理。此外，对原代足细胞的分析表明，-缺陷导致足细胞-GBM 相互作用受损和大量层粘连蛋白-α在足细胞中表达。我们的研究表明，由于-缺陷导致的足细胞-GBM 相互作用减弱，会在出生后通过持续的日常过滤对足细胞产生持续的机械应力，导致应激足细胞异位产生层粘连蛋白-α，从而中断 GBM 的处理。我们得出结论，Tns2 在足细胞-GBM 相互作用和肾小球滤过屏障的维持中发挥重要作用。
