USP13-HIF1α在低氧介导肺纤维化持续进展中的作用机制研究

特发性肺纤维化（IPF）是一种慢性、进行性致纤维化的间质性肺疾病，也是最常见且对人类健康危害最严重的特发性间质性肺炎。目前病因不明，发病研究不清。研究认为IPF发生发展过程中，上皮损伤与表型转化是启动因素，成纤维细胞活化及表型转化是IPF持续进展的推动因素。本研究从IPF肺组织局部低氧微环境出发，通过原代人肺成纤维细胞、基因敲除小鼠探讨在肺损伤过程中，低氧微环境通过USP13-HIFα途径调控肺成纤维细胞持续高表达HIF-1α，进而增强糖酵解，促进肺成纤维细胞持续增殖并表型转化，分泌大量细胞外基质，形成成纤维细胞灶，不断扩大纤维化范围，导致IPF持续进展。

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic interstitial lung disease, and is the most common idiopathic interstitial pneumonia that poses the greatest risk to human health. The current etiology is unknown and the pathogenesis is unclear. It is considered that the epithelial injury and conversion are the triggering factors in the development of IPF, and the fibroblasts activation and transformation are the driving factors for the continued progress of IPF. This study focus on the local hypoxia microenvironment of IPF lung tissues by primary human lung fibroblasts culture and knockout mice. It aims to investigate the mechanism of USP13-HIFα pathway which regulated lung fibroblasts continuous activation under hypoxia condition. Expression of HIF-1α enhances glycolysis, promoting lung fibroblasts continuous proliferation and transformation, secreting large amounts of ECM and forming fibroblast foci, resulting in continuously expansion of the extent of fibrosis and sustained progression of IPF.