MYBL2蛋白通过影响巨噬细胞的活化参与特发性肺纤维化发病的研究

异常的免疫调节在特发性肺纤维化（IPF）的发病中发挥重要作用，研究表明MYBL2分子参与了IPF发生发展的过程，但其具体的影响机制亟待进一步阐明。申请人通过预实验发现，MYBL2在IPF患者肺组织及肺泡灌洗液中表达增加，并且这种表达的增强主要集中于M2型巨噬细胞内；此外，小鼠巨噬细胞内Mybl2特异性敲除能显著减轻博来霉素诱导的肺纤维化程度，同时肺组织中还伴随明显减少的巨噬细胞的M2型活化水平。基于以上结果，本项目拟通过研究IPF患者肺组织中MYBL2的表达与IPF患者临床指标的相关性，探讨MYBL2在IPF发病机制中的作用；并进一步以巨噬细胞内Mybl2特异性敲除小鼠为研究工具，通过动物模型与细胞干预实验，阐明Mybl2对于巨噬细胞活化的影响及其机制以及由此对肺纤维化产生的影响。本研究的实施将进一步深化对IPF发病机制的认识，并可能为IPF的治疗发现新的干预靶点，具有至关重要的临床意义。

Abnormal immune regulation plays an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Studies have shown that MYBL2 is involved in the development of IPF, but its specific impact mechanism needs to be further elucidated. Through preliminary experiments, the applicant found that the expression of MYBL2 in the lung tissue and alveolar lavage fluid of IPF patients was significantly increased, and the enhancement of this expression was mainly concentrated in M2 macrophages. Besides, compared with control mice, mice specifically lacking Mybl2 in macrophages exhibited a slighter level of pulmonary fibrosis caused by bleomycin, accompanied by a significantly reduced level of alternative activation of macrophages. Based on the above experimental results, this project firstly intends to explore the role of MYBL2 in the pathogenesis of IPF by observing the correlation between the expression of MYBL2 in the lung tissues and the clinical symptoms of IPF patients. Secondly, experiments will be carried out in vivo and in vitro on the macrophage-specific Mybl2 knockout mice to clarify the effects of Mybl2 on macrophages activation and its mechanisms. The implementation of this study will further deepen the understanding of the pathogenesis of IPF, and may find new intervention targets for the treatment of IPF, which has vital clinical significance and irreplaceable social value.