Kyung Sun Young, Byun Kyung Hee, Yoon Jin Young, Kim Yu Jin, Lee Sang Pyo, Park Jeong-Woong, Lee Bong Hee, Park Jong Sook, Jang An Soo, Park Choon Sik, Jeong Sung Hwan
Department of Internal Medicine, Gachon University Gil Medical Center Incheon, Republic of Korea.
Department of Anatomy, Gachon University of Medicine and Science Incheon, Republic of Korea.
Int J Clin Exp Pathol. 2013 Dec 15;7(1):221-8. eCollection 2014.
Advanced glycation end products (AGEs) are associated with the pathogenesis of various diseases. AGEs induce excess accumulation of extracellular matrix and expression of profibrotic cytokines. In addition, studies on receptor for advanced glycation end products (RAGE) have shown that the ligand-RAGE interaction activates several intracellular signaling cascades associated with several fibrotic diseases. We investigated the expression of AGEs and RAGE in samples from patients with idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP). Lung tissues and plasma samples from patients with IPF (n=10), NSIP (n=10), and control subjects (n=10) were obtained. Expression of AGEs and RAGE was determined by immunofluorescence assay of lung tissue. Circulating AGEs were measured by Western blot and enzyme-linked immunosorbent assay. Lungs with IPF showed strong expression for both AGEs and RAGE compared to that in NSIP and controls. However, no difference in AGE or RAGE expression was observed in lungs with NSIP compared to that in the controls. Levels of circulating AGEs also increased significantly in lungs of patients with IPF compared to those with NSIP and normal control. Increased AGE-RAGE interaction may play an important role in the pathogenesis of IPF.
晚期糖基化终末产物（AGEs）与多种疾病的发病机制相关。AGEs可诱导细胞外基质过度积聚和促纤维化细胞因子的表达。此外，关于晚期糖基化终末产物受体（RAGE）的研究表明，配体与RAGE的相互作用可激活与多种纤维化疾病相关的多个细胞内信号级联反应。我们研究了特发性肺纤维化（IPF）和非特异性间质性肺炎（NSIP）患者样本中AGEs和RAGE的表达情况。获取了IPF患者（n = 10）、NSIP患者（n = 10）和对照受试者（n = 10）的肺组织和血浆样本。通过肺组织免疫荧光测定法确定AGEs和RAGE的表达。通过蛋白质免疫印迹法和酶联免疫吸附测定法检测循环中的AGEs。与NSIP和对照相比，IPF患者的肺组织中AGEs和RAGE均呈强表达。然而，与对照相比，NSIP患者的肺组织中未观察到AGE或RAGE表达的差异。与NSIP患者和正常对照相比，IPF患者肺组织中循环AGEs水平也显著升高。AGE-RAGE相互作用增强可能在IPF的发病机制中起重要作用。
