MIR107介导B淋巴细胞自噬在肾移植术后体液免疫排斥反应中的作用机制研究

Renal transplantation is an ideal method for the treatment of patients with end-stage renal disease. In renal transplant patients, despite the current short-term human kidney survival rate has improved significantly, the long-term survival rate is still not satisfactory. Graft rejection is considered to be the main factor affecting the long-term survival of transplanted kidney. Antibody mediated rejection (ABMR) is one of the important mechanisms of rejection after renal transplantation. At present, the treatment effect for chronic rejection mediated by antibody is not ideal.Therefore, clarifying the mechanism of ABMR to reveal the pathogenic mechanism, has the important theory and clinical significance for the development of new and effective drugs in the treatment of ABMR. This project aims to regulate autophagy pathway for MIR107 through the signaling protein ATG12 and up regulation of autophagy, leading to B lymphocytes mature for differentiation and antibody production. Taking the occurrence of ABMR as a starting point, respectively, in vivo, in vitro, the up-regulated or down regulated MIR107, observe the changes of B lymphocyte differentiation ability and autophagy，the impact of autophagy on the regulation of the differentiation and maturation of B lymphocyte. To investigate the effect of "mode of ABMR, miRNA and Autophagy", in order to clarify the mechanism of MIR107 in regulating B lymphocytes autophagy and ABMR, provides clues for finding new therapeutic targets.

肾移植是终末期肾脏病患者的理想治疗方法，尽管目前肾移植患者短期人-肾存活率有明显改善，但长期存活率仍不让人满意。移植排斥反应被认为是影响移植肾长期存活的主要因素。而抗体介导的排斥反应（ABMR）是肾移植术后排斥反应的重要机制之一。目前对于抗体介导的慢性排斥反应治疗效果并不理想。因此, 深入阐明ABMR的确切机制对揭示其致病机理、发展新的有效的治疗ABMR的药物具有重要理论和临床意义。本项目拟针对MIR107通过调节自噬通路中的信号蛋白ATG12而上调自噬，导致B淋巴细胞成熟分化和抗体的产生，进而发生ABMR为切入点，分别在体内、体外，通过上调或下调MIR107，观察B淋巴细胞自噬和成熟分化能力的变化，以及自噬对B淋巴细胞成熟分化的调控，探讨“ABMR、miRNA与Autophagy”的作用模式，以期阐明MIR107在B淋巴细胞自噬调节与ABMR发生的机制，为寻找新的治疗药物靶点提供线索。

肾移植是终末期肾脏病患者的理想治疗方法，尽管目前肾移植患者短期人-肾存活率有明显改善，但长期存活率仍不让人满意。移植排斥反应被认为是影响移植肾长期存活的主要因素。而抗体介导的排斥反应（ABMR）是肾移植术后排斥反应的重要机制之一。目前对于抗体介导的慢性排斥反应治疗效果并不理想。因此, 我们深入阐明ABMR的确切机制对揭示其致病机理、发展新的有效的治疗ABMR的药物具有重要理论和临床意义。本项目针对MIR107通过调节自噬通路中的信号蛋白ATG12而上调自噬，导致B淋巴细胞成熟分化和抗体的产生，进而发生ABMR为切入点，分别在体内、体外，通过上调或下调MIR107，观察B淋巴细胞自噬和成熟分化能力的变化，以及自噬对B淋巴细胞成熟分化的调控，探讨“ABMR、miRNA与Autophagy”的作用模式，阐明了MIR107在B淋巴细胞自噬调节与ABMR发生的机制，为寻找新的治疗药物靶点提供线索。