间质纤维化病变及小管萎缩于移植肾中常见，并严重影响长期肾功能的维持，造成了医疗资源的严重消耗。整合素连接激酶(Integrin Linked Kinase, ILK)作为重要的交互位点，介导TGF-β1/Smad和Wnt/β-catenin途径协同作用于胚胎发育、纤维化和肿瘤进展等领域，但ILK促纤维化进程在移植肾领域尚未报道。本项目力求阐明ILK在慢性移植肾纤维化发生和进展中的关键作用。具体研究内容包括三个方面：(1)利用染色质免疫共沉淀-下一代测序联用和邻位连接等技术，明确ILK在慢性移植肾纤维化的作用机制以及与TGF-β1和Wnt/β-catenin途径转录因子的相互作用；(2)以活体或心脏死亡的ILK条件性敲除小鼠作为供肾来源，探讨不同类型供肾纤维化的异同；(3)利用慢病毒在体转染技术，介导野生型小鼠肾脏ILK表达沉默，评估ILK在移植肾进程性纤维化防治中的潜在应用价值。

Renal interstitial fibrosis and tubular atrophy are common in transplant kidneys, which severely affect long-term renal function and induce medical resource consumption. Wnt/β-catenin and TGF-β1 signaling pathway are involved in multiple EMT associated processes such as embryogenesis, fibrosis and tumor progression, where Integrin Linked Kinase (ILK) plays a vital role in the extensive cross-talk. ILK mediating the cross-talk between two pathways in the field of renal transplantation has not been reported before without clear results regarding the mechanisms. In this proposed research project we aim to clarify the key role of ILK in the cross- talk between the two pathways in three aspects: (1) Utilizing Chromatin Immunoprecipitation-The Next Generation Sequencing and Duolink Proximity Ligation Assay (PLA) to explore the interaction between ILK and key transcription factors. (2) Evaluating Living-donor (LD) and Donation after Cardiac Death (DCD) allografts in mice renal transplantation models. (3) Applying Lentivirus infection to interfere gene expression so as to evaluate the potential treatment target of ILK in allograft fibrosis.