Proteinuria, the presence of high molecular weight proteins in the urine, is a primary indicator of chronic kidney disease. Proteinuria results from increased molecular permeability of the glomerular filtration barrier combined with saturation or defects in tubular protein reabsorption. Any solute that passes into the glomerular filtrate traverses the glomerular endothelium, the glomerular basement membrane, and the podocyte slit diaphragm. Damage to any layer of the filter has reciprocal effects on other layers to increase glomerular permeability. The GBM is thought to act as a compressible ultrafilter that has increased molecular selectivity with increased pressure due to compression that reduced the porosity of the GBM with increased pressure. In multiple forms of chronic kidney disease, crosslinking enzymes are upregulated and may act to increase GBM stiffness. Here we show that enzymatically crosslinking porcine GBM with transglutaminase increases the stiffness of the GBM and mitigates pressure-dependent reductions in molecular sieving coefficient. This was modeled mathematically using a modified membrane transport model accounting for GBM compression. Changes in the mechanical properties of the GBM may contribute to proteinuria through pressure-dependent effects on GBM porosity.

中文翻译：

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转谷氨酰胺酶介导的肾小球基底膜硬化通过减少压力来减轻压力引起的分子筛系数的降低


蛋白尿，即尿液中存在高分子量蛋白质，是慢性肾脏病的主要指标。蛋白尿是由肾小球滤过屏障的分子通透性增加以及肾小管蛋白质重吸收的饱和或缺陷引起的。任何进入肾小球滤液的溶质都会穿过肾小球内皮、肾小球基底膜和足细胞裂隙隔膜。过滤器任何层的损坏都会对其他层产生相互作用，从而增加肾小球的通透性。 GBM被认为是一种可压缩的超滤器，随着压力的增加，分子选择性也随之增加，因为压缩会随着压力的增加而减少GBM的孔隙率。在多种形式的慢性肾病中，交联酶上调，可能会增加 GBM 硬度。在这里，我们表明，用转谷氨酰胺酶酶交联猪 GBM 会增加 GBM 的硬度，并减轻分子筛系数的压力依赖性降低。这是使用考虑 GBM 压缩的改良膜传输模型进行数学建模的。 GBM 机械性能的变化可能通过对 GBM 孔隙率的压力依赖性影响而导致蛋白尿。