Abstract：
Desmosomes are multi-protein cell-cell adhesion structures supporting cell stability and mechanical stress resilience of tissues, best described in skin and heart. The kidney is exposed to various mechanical stimuli and stress, yet little is known about kidney desmosomes. In healthy kidneys, we found desmosomal proteins located at the apical-junctional complex in tubular epithelial cells. In four different animal models and patient biopsies with various kidney diseases, desmosomal components were significantly upregulated and partly miss-localized outside of the apical-junctional complexes along the whole lateral tubular epithelial cell membrane. The most upregulated component was desmoglein-2 (Dsg2). Mice with constitutive tubular epithelial cell-specific deletion of Dsg2 developed normally, and other desmosomal components were not altered in these mice. When challenged with different types of tubular epithelial cell injury (unilateral ureteral obstruction, ischemia-reperfusion, and 2,8-dihydroxyadenine crystal nephropathy), we found increased tubular epithelial cell apoptosis, proliferation, tubular atrophy, and inflammation compared to wild-type mice in all models and time points. In vitro, silencing DSG2 via siRNA weakened cell-cell adhesion in HK-2 cells and increased cell death. Thus, our data show a prominent upregulation of desmosomal components in tubular cells across species and diseases and suggest a protective role of Dsg2 against various injurious stimuli.
摘要：
Desmosomes是多蛋白细胞-细胞粘附结构，支持组织的细胞稳定性和机械应力弹性；在皮肤和心脏中最好的描述。肾脏受到各种机械刺激和压力，然而对肾桥粒知之甚少。在健康的肾脏中，我们发现桥粒蛋白位于肾小管上皮细胞的顶端连接复合体。在四种不同的动物模型和患有各种肾脏疾病的患者活检中，桥粒成分显着上调，部分缺失位于整个外侧肾小管上皮细胞膜的顶端连接复合物之外。最上调的组分是桥粒蛋白-2(Dsg2)。在这些小鼠中，具有组成型肾小管上皮细胞特异性Dsg2缺失的小鼠发育正常，其他桥粒成分未改变。当受到不同类型的肾小管上皮细胞损伤（单侧输尿管梗阻，缺血再灌注,和2,8-二羟基腺嘌呤晶体肾病），我们发现肾小管上皮细胞凋亡增加，扩散,肾小管萎缩,在所有模型和时间点与野生型小鼠相比和炎症。体外，通过siRNA沉默DSG2会削弱HK-2细胞中的细胞-细胞粘附并增加细胞死亡。因此，我们的数据显示，跨物种和疾病的肾小管细胞中的桥粒成分明显上调，并表明Dsg2对各种有害刺激具有保护作用。
