Role of Lung Apolipoprotein A-I in Idiopathic Pulmonary Fibrosis: Antiinflammatory and Antifibrotic Effect on Experimental Lung Injury and Fibrosis

作者：Tae Hoon Kim, Yoo Hoon Lee, Kyung Hun Kim, Shin Hwa Lee, Ji Yeon Cha, Eun Kyoung Shin, Seok Jung, An‐Soo Jang, Sung‐Woo Park, Soo Taek Uh, Young‐Hoon Kim, Jai Soung Park, Hwa Gyoun Sin, Wook Youm, Eun Suk Koh, Sun Young Cho, Young Ki Paik, Tai Youn Rhim, Choon‐Sik Park · 发表于：American Journal of Respiratory and Critical Care Medicine · 年份：2010 · DOI：10.1164/rccm.200905-0659oc · 被引用次数：125 · 研究领域：Clusterin in disease pathology、Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Caveolin-1 and cellular processes

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is caused by alterations in expression of proteins involved in multiple pathways, including matrix deposition, inflammation, injury, and repair. OBJECTIVES: To understand the pathogenic changes in lung protein expression in IPF and to evaluate apolipoprotein (Apo) A-I as a candidate therapeutic molecule. METHODS: Two-dimensional electrophoresis was adopted for differential display proteomics. Reverse-transcriptase polymerase chain reaction, Western blotting, immunohistochemical staining, and ELISA were performed for identification and quantitative measurement of Apo A-I in bronchoalveolar lavage fluids from subjects with IPF and experimental bleomycin-induced mice. MEASUREMENTS AND MAIN RESULTS: Sixteen protein spots showed differences in relative intensity between IPF (n = 14) and healthy control subjects (n = 8). Nano liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed increase of haptoglobulin and decrease of alpha(1)-antitrypsin, alpha(1)-antichymotrypsin, macrophage capping protein, angiotensinogen, hemoglobin chain B, Apo A-I, clusterin, protein disulfide isomerase A3, immunoglobulin, and complement C4A in IPF compared with normal control subjects (P = 0.006-0.044). Apo A-I concentrations were lower in bronchoalveolar lavage fluids from subjects with IPF (n = 28) than in normal control subjects (n = 18; P < 0.01). In bleomycin-treated mice, Apo A-I protein in BALF was lower than that in sham-treated control a...