Intratubular hydrodynamic forces influence tubulointerstitial fibrosis in the kidney.
Intratubular hydrodynamic forces influence tubulointerstitial fibrosis in the kidney.
复制标题
DOI：
10.1097/mnh.0b013e32833327f3
复制
发表时间：
2010-01
影响因子：
3.2
通讯作者：
Flores D
中科院分区：
文献类型：
--
作者：
Rohatgi R;Flores D
肾上皮细胞以立即转导事件（例如，离子通道的激活），中间生物反应（例如，基因表达的变化），和长期细胞适应（例如，蛋白质表达）。进行性肾脏疾病的特征在于肾小球流体动力学紊乱，导致肾小球硬化，但是，对管内生物力学力如何导致肾小管-肾小管炎症和纤维化知之甚少。阻塞性尿路病的体内和体外模型表明，肾小管牵张诱导转化生长因子β-1（TGF β-1）的稳健表达、肾小管凋亡的激活和NF-κ B信号传导的诱导，这些都有助于炎症和纤维化环境。与肾单位丢失相关的非梗阻性结构性肾脏疾病遵循以单个肾单位肾小球滤过率和肾小管流速代偿性增加为特征的过程。由此产生的小管流体剪切应力（FSS）的增加降低了组织纤溶酶原激活剂和尿激酶的酶活性，从而减少了细胞外基质的分解。在高钠饮食摄入模型中，肾小管流量增加，尿TGF β-1浓度和肾丝裂原活化蛋白激酶活性增加。总之，管内生物力学力，拉伸和FSS，产生细胞内信号和基因表达的变化，有助于阻塞性和非阻塞性肾脏疾病的病理生物学。
Renal epithelial cells respond to mechanical stimuli with immediate transduction events (e.g., activation of ion channels), intermediate biological responses (e.g., changes in gene expression), and long term cellular adaptation (e.g., protein expression). Progressive renal disease is characterized by disturbed glomerular hydrodynamics that contributes to glomerulosclerosis, but, how intra-tubular biomechanical forces contribute to tubulo-interstital inflammation and fibrosis is poorly understood. In vivo and in vitro models of obstructive uropathy demonstrate that tubular stretch induces robust expression of transforming growth factor β-1 (TGFβ-1), activation of tubular apoptosis, and induction of NF-κB signaling which contribute to the inflammatory and fibrotic milieu. Non-obstructive structural kidney diseases associated with nephron loss follow a course characterized by compensatory increases of single nephron glomerular filtration rate and tubular flow rate. Resulting increases in tubular fluid shear stress (FSS) reduce tissue-plasminogen activator and urokinase enzymatic activity which diminishes breakdown of extracellular matrix. In models of high dietary Na intake, which increase tubular flow, urinary TGFβ-1 concentrations and renal mitogen activated protein kinase activity are increased. In conclusion, intra-tubular biomechanical forces, stretch and FSS, generate changes in intracellular signaling and gene expression that contribute to the pathobiology of obstructive, and non-obstructive kidney disease.