细胞生物学
下调和上调
桥粒蛋白
病理
肾
细胞
医学
生物
钙粘蛋白
内分泌学
生物化学
遗传学
基因
作者
Tong Xu,Lea Herkens,Ting Jia,Barbara M. Klinkhammer,Sebastian Kant,Claudia A. Krusche,Eva Miriam Buhl,Sikander Hayat,Jürgen Floege,Pavel Strnad,Rafael Kramann,Sonja Djudjaj,Peter Boor
标识
DOI:10.1016/j.kint.2024.01.037
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI