HIV infection changes glomerular podocyte cytoskeletal composition and results in distinct cellular mechanical properties.
HIV infection changes glomerular podocyte cytoskeletal composition and results in distinct cellular mechanical properties.
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DOI：
10.1152/ajprenal.00246.2006
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发表时间：
2007-02
期刊：
影响因子：
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通讯作者：
R. Tandon;I. Levental;C. Huang;F. Byfield;J. Ziembicki;J. Schelling;L. Bruggeman;J. Sedor;P. Janmey;R. Miller
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文献类型：
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作者：
R. Tandon;I. Levental;C. Huang;F. Byfield;J. Ziembicki;J. Schelling;L. Bruggeman;J. Sedor;P. Janmey;R. Miller
足细胞除了为肾小球形成选择性滤过屏障外，还通过对抗扩张的血流动力学力量维持肾小球的毛细血管结构。为了了解细胞骨架特性与足细胞力学特性的关系，我们研究了条件永生化野生型(WT)小鼠足细胞和HIV相关肾病(HIVAN)小鼠模型的足细胞中丝蛋白的表达和分布，并测量了细胞膜的变形性。在WT细胞中，细丝蛋白和F-肌动蛋白定位于外周和突出的应力纤维中。在HIVAN细胞中，细丝蛋白表达减少，应激纤维稀疏。在微量吸入法中，HIVAN细胞在最小负压下破裂。原子力显微镜显示WT细胞的硬度为17kpa，而HIVAN细胞的硬度为4kpa。这些结果表明，WT和HIVAN足细胞的力学性能明显不同，这与它们细胞骨架的组成和排列方式的不同是一致的。WT足细胞的力学性质表明，这些细胞比HIVAN足细胞更能维持毛细血管的完整性，并提示细胞骨架的病理组装是HIVAN的一个机制。
In addition to forming the selective filtration barrier for the renal glomerulus, podocytes maintain glomerular capillary architecture by opposing distending hemodynamic forces. To understand the relationship of cytoskeletal properties and the mechanical characteristics of podocytes, we studied filamin expression and distribution and measured cell membrane deformability in conditionally immortalized wild-type (WT) mouse podocytes, and in podocytes derived from a mouse model of HIV-associated nephropathy (HIVAN). In the WT cells, filamin and F-actin were localized at the periphery and in prominent stress fibers. In the HIVAN cells, filamin expression was reduced, and stress fibers were sparse. In a microaspiration assay, HIVAN cells ruptured under minimal negative pressure. Atomic force microscopy demonstrated that the WT cells had a stiffness of 17 kPa, whereas the value for the HIVAN cells was 4 kPa. These results demonstrate that the mechanical properties of WT and HIVAN podocytes are markedly different in a manner that is consistent with differences in the composition and arrangement of their cytoskeletons. The mechanical properties of the WT podocytes suggest that these cells can better maintain capillary integrity than the HIVAN podocytes and implicate pathological assembly of the cytoskeleton as a mechanism of HIVAN.