Relationship of and cross-talk between physical and biologic properties of the glomerulus.
Relationship of and cross-talk between physical and biologic properties of the glomerulus.
复制标题
DOI：
10.1097/mnh.0000000000000138
复制
发表时间：
2015-07
影响因子：
3.2
通讯作者：
Janmey PA
中科院分区：
文献类型：
--
作者：
Miller RT;Janmey PA
细胞和组织必须对物理力作出反应。细胞存在于由其基质、基质接触、细胞-细胞接触和细胞骨架结构决定的弹性环境中。我们讨论了细胞弹性环境的决定因素及其在肾小球疾病中的潜在作用。弹性环境足以诱导和维持包括肌成纤维细胞在内的细胞的分化状态。新的实验技术允许精确测量正常和患病组织和细胞的弹性特性，并分析细胞行为和细胞骨架结构对机械和弹性刺激的反应。肾小球在几种疾病模型的病程早期变软，但晚期的特征是硬度增加和纤维化，伴有器官功能丧失。在肝纤维化、动脉疾病和肿瘤学方面的研究表明，赖氨酰氧化酶引起的胶原交联增加（疾病的早期步骤）可导致组织硬度充分增加，从而改变细胞行为，导致疾病进展。细胞和组织的弹性环境提供了发育、分化和疾病的基本信号。确定决定肾小球细胞弹性环境的机制将补充其他方法，以减少病理性纤维化和组织功能丧失。
Cells and tissues must respond to physical forces. Cells exist in an elastic environment determined by their matrix, matrix contacts, cell-cell contacts, and cytoskeletal structure. We discuss the determinants of the elastic environment of cells and its potential roles in glomerular disease. Elastic environment is sufficient to induce and maintain the differentiated state of cells including myofibroblasts. New experimental techniques permit precise measurement of the elastic characteristics of normal and diseased tissues and cells, and analysis of cell behavior and cytoskeletal structure in response to mechanical and elastic stimuli. Glomeruli become soft early in the course of several disease models, yet late stages are characterized by increased stiffness and fibrosis with loss of organ function. Work in hepatic fibrosis, arterial disease, and oncology demonstrate that increased collagen crosslinking by lysyl oxidase, an early step in the diseases, can result in a sufficient increase in tissue stiffness to alter cell behavior leading to disease progression. The elastic environment of cells and tissues provides essential signals in development, differentiation, and disease. Identifying the mechanisms that determine the elastic environment of glomerular cells will complement other approaches to reduce pathologic fibrosis and loss of tissue function.