肺泡上皮细胞RUNX1通过线粒体调控CTGF对特发性肺纤维化的影响

肺泡上皮细胞损伤及异常修复是特发性肺纤维化（idiopathic pulmonary fibrosis，IPF）发生发展的核心环节，但机制不明。我们前期发现RUNX1是肺泡上皮细胞维持正常功能的一种关键调控蛋白。定向敲除肺泡上皮细胞RUNX1不仅会影响线粒体的结构和功能，还可负调控CTGF的表达。基于此，我们提出“肺泡上皮细胞RUNX1通过调控线粒体影响CTGF进而参与IPF的发生与发展”科学假说。为证实上述假说，我们拟利用IPF患者肺组织样本、肺泡上皮细胞RUNX1定向敲除/上调小鼠肺纤维化模型，以线粒体和CTGF为核心指标，利用多组学整合分析技术及经典、成熟的分子生物细胞学等方法，分别从体内和体外、正反两方面，明确“RUNX1/线粒体/CTGF”通路在IPF中的作用及调控机制。通过上述研究将揭示新的IPF病理机制，为临床开发新的IPF精准治疗策略奠定基础。

Alveolar epithelial cells injury and abnormally repair are the key to idiopathic pulmonary fibrosis (IPF), but the mechanism is not yet clear. Our previous studies have shown that RUNX1 is a key regulatory protein which maintains the normal function of alveolar epithelial cells. Conditional deletion of RUNX1 in alveolar epithelial cells not only affect the structure and function of mitochondria, but also negatively regulate the expression of CTGF. Based on this, we propose the hypothesis that RUNX1 of alveolar epithelial cells affects CTGF through mitochondria to participate in IPF. We used RUNX1 knockout mice and overexpressed mice to construct a mouse model of pulmonary fibrosis by intratracheal infusion of low-dose bleomycin. And measure the structure and function of mitochondrion as well as the expression of CTGF. Using multi-omics integration analysis and the classical and matured biotechnologies to figure out the mechanism “RUNX1/mitochondrion/CTGF pathway” in IPF from in vivo and in vitro, forward and reverse. This study will clarify the mechanism of “RUNX1/mitochondria/CTGF ”pathway in IPF, and lay the foundation for clinical development of novel therapeutic target for IPF patients.