基于microRNA调控网络的应力促进组织工程膀胱细胞功能化研究

构建功能化组织工程膀胱一直是业界研究的焦点，但缺乏具有正常表型和功能的种子细胞限制了组织工程膀胱的发展和临床应用。血管及骨材料的研究表明：要促进细胞功能正常化，适当的应力刺激十分重要，且mi-RNAs参与控制这一生物学适应性过程。膀胱本身处于流体应力环境，应力同样是膀胱发育中的重要诱导因素。我们前期研究已证实膀胱种子细胞在应力状态下，关键功能基因的表达出现，相关mi-RNAs表达谱改变。因此，课题组首次应用生物力学诱导膀胱细胞功能成熟化，并提出mi-RNAs是介导这一生物学过程的关键要素的假说。本项目拟对膀胱细胞施加不同特性的应力，观察机械应力对膀胱细胞功能的具体影响，并证实mi-RNAs及其下游整合素信号、有丝分裂原激动蛋白激酶(MAPKs) 等目标信号通路网络在细胞功能转变中的定位和作用，构建应力诱导膀胱细胞功能成熟化的mi-RNAs调控网络，从而为构建功能化组织工程膀胱奠定基础.

Engineering of functional bladder is one of important challenges in urological field; however, the clinical application of tissue engineering bladder is limited by shortage of bladder cell with normal phenotype and function. The studies from engineering vascular and bone materials have demonstrated that optimal physiological stress is requirement for inducing the normalization of cellular function, which mi-RNAs involved in this biological process. Bladder is positioned in a fluid physiological stress environment, thus the stress should be one of significant elements in development of bladder. Our preliminary results found that key functional genes of bladder cells appeared, contractility of bladder cell was enhanced and profile of mi-RNAs was altered under cyclic stress. Therefore, we try to induce the normalization of bladder cellular function by biomechanics, and propose the hypothesis that mi-RNAs is one of key factors in this process. The study will apply different kinds of mechanical stimuli to bladder cells, observe the effect of physiological stress on cellular function, and identify the location and role of mi-RNAs and its downstream target signals such as integrin and MAPKs in network of signal pathway, and then construct the network that mi-RNAs regulate functional normalization of bladder cells under physiological stress, which lay the ground for construction of functional tissue engineering bladder.