晚期糖基化终产物受体(RAGE)主要在肺部表达,以细胞膜型(mRAGE)和可溶型(sRAGE)形式存在。RAGE与肺间质纤维化密切相关，然而RAGE的作用尚不清楚。我们既往的研究发现RAGE基因敲除鼠没有出现博莱霉素诱导的肺间质纤维化，而IPF患者血清内源性分泌的sRAGE减少。由此我们提出肺损伤后，肺内RAGE表达向mRAGE偏移，sRAGE减少，导致mRAGE/sRAGE失衡，促使肺间质纤维化发生的假说。为验证这一假说，我们将在博莱霉素肺纤维化小鼠模型上，观察肺组织mRAGE和sRAGE的动态变化,并予以sRAGE干预，证明肺纤维化时mRAGE/sRAGE失衡，纠正sRAGE丢失对肺纤维化的抑制作用。结合sRAGE对促纤维化因子变化的影响以及对原代肺泡II型上皮细胞EMT变化的影响，探讨sRAGE对肺纤维化保护作用机制。为建立肺间质纤维化的预测指标并为提供新的治疗靶点奠定理论基础。

The receptor for advanced glycation end-products (RAGE) is highly expressed in the lung. RAGE is involved in the pathogenesis of pulmonary fibrosis, however, it remains unclear about the role and mechanism of the different kinds of RAGE. We found that RAGE deficent mice protected from bleomycin-induced lung fibrosis, and we also found that lower serum level of endogenous secretory RAGE in the patients with IPF than in health. Therefore, we propose that lung injury polarizes the expression of RAGE toward membrane RAGE (mRAGE) in the lung, which leads to the decreased expression of soluble RAGE (sRAGE). Subsequently, the imbalance of mRAGE/sRAGE leads to accelerate the occurrence of pulmonary fibrosis. To clarify the loss of sRAGE is the pathogenesis of fibrosis, we will evaluate the expression of mRAGE and sRAGE in bleomycin-induced lung fibrosis in mice. To evaluate the protective effect of sRAGE on bleomycin-induced fibrosis, BAL fluid will be collected for cell counting and measurements of lung permeability, and profibrotic cytokines of TGF-beta and PDGF after intratracheal bleomycin in the mice with or without intraperitoneal administration of sRAGE. To evaluate the inhibit effect of sRAGE on epithelial-mesenchymal transtion process, alveolar type II epithelial cells will be isolated from mice and exposes to HMGB1 with or without sRAGE then will be checked the changes of cell phenotypes. This study will demonstrate that sRAGE plays a protective role in pathogenesis of bleomycin-induced fibrosis and will explore the underlying mechanism. sRAGE is expected to be a new biomarker of fibrosis and a therapeutic target for pulmonary fibrosis.