靶向抑制ILK调控晶状体上皮细胞EMT信号通路的实验研究

Posterior capsular opacification (PCO) is the major complication arising after cataract treatment. PCO occurs when the lens epithelial cells remaining following surgery undergo an epithelial–mesenchymal transition (EMT) into migratory myofibroblasts. transforming growth factor beta (TGF-β) signalling is crucial for PCO deriving from the EMT of LECs, and Integrins are key mediators of ECM signals to induce EMT. Increasingly, studies are being directed to investigating the signaling pathways that TGF-β and integrins modulate jointly and have identified integrin-linked kinase (ILK) as common downstream kinase that mediate proliferation, differentiation and morphological changes in PCO. In the study, we designed the siRNA of integrin-linked kinase (ILK) to evaluate the effect of targeting si-ILK on the proliferation , adhesion and migration of LECs, and investigate the relationship and change involved signaling pathways including Smad、P13K. Lastly, we verificated the effect of down-regulated expression of ILK on PCO by a mouse model of cataract surgery. As therapeutics targeting, ILK possessed the potential to be developed as a therapeutic agent for PCO.

白内障术后晶状体上皮细胞（LECs）发生上皮-间质化生(EMT)的过程实质上是后发性白内障（PCO）发生发展的主要病理基础，转化生长因子-β（TGF-β）是LECs发生EMT的始动调节因子；整合素则是细胞外基质诱导EMT的媒介；而整合素连接激酶（ILK）恰是二者在EMT过程中的交集因子。结合其他领域基础研究的最新进展和前期工作，本研究选择ILK作为新的干预靶点，利用RNA干扰技术，检测下调ILK表达对LECs生物学功能的影响；观察相关信号通路(Smad、P13K)的变化；了解ILK和相关信号分子在细胞EMT中的关系；明确ILK在EMT中的信号调控作用；最后通过动物实验验证下调ILK的表达在防治PCO中的作用。本研究从细胞外刺激、细胞形态功能变化、细胞内信号传导等多方面阐述PCO发生的分子机制，为治疗PCO提供理论依据及准确的药物靶点。

白内障术后晶状体上皮细胞（LECs）发生上皮-间质化生(EMT)的过程实质上是后发性白内障（PCO）发生发展的主要病理基础，转化生长因子-β（TGF-β）是LECs发生EMT的始动调节因子；整合素则是细胞外基质诱导EMT的媒介；而整合素连接激酶（ILK）恰是二者在EMT过程中的交集因子。结合其他领域基础研究的最新进展和前期工作，本研究选择ILK作为新的干预靶点，利用RNA干扰技术，检测下调ILK表达对LECs生物学功能的影响；观察相关信号通路(Smad、P13K)的变化；了解ILK和相关信号分子在细胞EMT中的关系；明确ILK在EMT中的信号调控作用；最后通过动物实验验证下调ILK的表达在防治PCO中的作用。本研究从细胞外刺激、细胞形态功能变化、细胞内信号传导等多方面阐述PCO发生的分子机制，为治疗PCO提供理论依据及准确的药物靶点。