https://scholars.lib.ntu.edu.tw/handle/123456789/480701
標題: | PlGF mediates neutrophil elastase-induced airway epithelial cell apoptosis and emphysema | 作者: | HSIN-HAN HOU Cheng S.-L. KUEI-PIN CHUNG SHU-CHEN WEI PO-NIEN TSAO Lu H.-H. HAO-CHIEN WANG CHONG-JEN YU |
公開日期: | 2014 | 出版社: | BioMed Central Ltd. | 卷: | 15 | 期: | 1 | 起(迄)頁: | 106 | 來源出版物: | Respiratory Research | 摘要: | Background: Chronic pulmonary obstructive disease (COPD) has become the fourth leading cause of death worldwide. Cigarette smoking induces neutrophil elastase (NE) and contributes to COPD, but the detailed mechanisms involved are not fully established. In an animal model of pulmonary emphysema, there are increased expressions of placenta growth factor (PlGF) and lung epithelial (LE) cell apoptosis. This study hypothesized that excessive NE may up-regulate PlGF and that PlGF-induced LE apoptosis mediates the pathogenesis of pulmonary emphysema. Methods: Human bronchial epithelial cells, BEAS-2B, and primary mouse type II alveolar epithelial cells were treated with NE. The PlGF promoter activity was examined by luciferase activity assay, while PlGF expression and secretion were evaluated by RT-PCR, Western blotting, and ELISA. Both cell lines were treated with PlGF to evaluate its effects and the downstream signaling pathways leading to LE cell apoptosis. PlGF knockout and wild-type mice were instilled with NE to determine the roles of PlGF and its downstream molecules in NE-promoted mice pulmonary apoptosis and emphysema phenotype. Results: The transcriptional factor, early growth response gene-1, was involved in the NE-promoted PlGF promoter activity, and the expression and secretion of PlGF mRNA and protein in LE cells. PlGF-induced LE cell apoptosis and NE-induced mice pulmonary apoptosis and emphysema were mediated by the downstream c-Jun N-terminal kinase (JNK) and protein kinase C (PKC)δ signaling pathways. Conclusion: The NE-PlGF-JNK/PKCδ pathway contributes to the pathogenesis of LE cell apoptosis and emphysema. PlGF and its downstream signaling molecules may be potential therapeutic targets for COPD. ? Hou et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84927935652&doi=10.1186%2fs12931-014-0106-1&partnerID=40&md5=ab4c926277d21db524db707341d3c0be https://scholars.lib.ntu.edu.tw/handle/123456789/480701 |
ISSN: | 1465-9921 | DOI: | 10.1186/s12931-014-0106-1 | SDG/關鍵字: | early growth response factor 1; leukocyte elastase; messenger RNA; placental growth factor; protein kinase C delta; stress activated protein kinase; early growth response factor 1; EGR1 protein, human; Egr1 protein, mouse; leukocyte elastase; placenta protein; placental growth factor; PRKCD protein, human; Prkcd protein, mouse; protein kinase C delta; stress activated protein kinase; animal cell; animal experiment; animal model; animal tissue; apoptosis; Article; bronchus mucosa; controlled study; early growth response gene 1; enzyme linked immunosorbent assay; epithelium cell; gene; gene expression; human; human cell; luciferase assay; lung alveolus epithelium cell; lung emphysema; male; mouse; nonhuman; pathogenesis; phenotype; promoter region; protein expression; reverse transcription polymerase chain reaction; signal transduction; Western blotting; wild type; animal; C57BL mouse; cell line; disease model; dose response; drug effects; enzymology; genetic transfection; genetics; immunology; knockout mouse; lung alveolus cell; lung emphysema; metabolism; pathology; signal transduction; time factor; upregulation; Animals; Apoptosis; Cell Line; Disease Models, Animal; Dose-Response Relationship, Drug; Early Growth Response Protein 1; Humans; JNK Mitogen-Activated Protein Kinases; Leukocyte Elastase; Male; Mice, Inbred C57BL; Mice, Knockout; Pneumocytes; Pregnancy Proteins; Promoter Regions, Genetic; Protein Kinase C-delta; Pulmonary Emphysema; Signal Transduction; Time Factors; Transfection; Up-Regulation |
顯示於: | 口腔生物科學研究所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。