https://scholars.lib.ntu.edu.tw/handle/123456789/545687
標題: | Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol alleviates elastase-induced emphysema in a mouse model | 作者: | Chen Y.-B. Lan Y.-W. Chen L.-G. Huang T.-T. Choo K.-B. Cheng W.T.K. Lee, Hsuan-Shu Chong K.-Y. |
關鍵字: | Emphysema; Hsp70 promoter; Mouse model; Resveratrol; Stem cell-based gene therapy; VEGFA | 公開日期: | 2015 | 出版社: | Cell Stress and Chaperones | 卷: | 20 | 期: | 6 | 起(迄)頁: | 979-989 | 來源出版物: | Cell Stress and Chaperones | 摘要: | Chronic obstructive pulmonary disease (COPD) is a sustained blockage of the airways due to lung inflammation occurring with chronic bronchitis and/or emphysema. Progression of emphysema may be slowed by vascular endothelial growth factor A (VEGFA), which reduces apoptotic tissue depletion. Previously, authors of the present report demonstrated that cis-resveratrol (c-RSV)-induced heat-shock protein 70 (HSP70) promoter-regulated VEGFA expression promoted neovascularization of genetically modified mesenchymal stem cells (HSP-VEGFA-MSC) in a mouse model of ischemic disease. Here, this same stem cell line was evaluated for its protective capacity to alleviate elastase-induced pulmonary emphysema in mice. Results of this study showed that c-RSV-treatment of HSP-VEGFA-MSC exhibited synergy between HSP70 transcription activity and induced expression of anti-oxidant-related genes when challenged by cigarette smoke extracts. Eight weeks after jugular vein injection of HSP-VEGFA-MSC into mice with elastase-induced pulmonary emphysema followed by c-RSV treatment to induce transgene expression, significant improvement was observed in respiratory functions. Expression of VEGFA, endogenous nuclear factor erythroid 2-related factor (Nrf 2), and manganese superoxide dismutase (MnSOD) was significantly increased in the lung tissues of the c-RSV-treated mice. Histopathologic examination of treated mice revealed gradual but significant abatement of emphysema and restoration of airspace volume. In conclusion, the present investigation demonstrates that c-RSV-regulated VEGFA expression in HSP-VEGFA-MSC significantly improved the therapeutic effects on the treatment of COPD in the mouse, possibly avoiding side effects associated with constitutive VEGFA expression. ? 2015, Cell Stress Society International. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84943356927&doi=10.1007%2fs12192-015-0627-7&partnerID=40&md5=ed5407b6fcb4368346f191ff5d1c8642 https://scholars.lib.ntu.edu.tw/handle/123456789/545687 |
ISSN: | 1355-8145 | DOI: | 10.1007/s12192-015-0627-7 | SDG/關鍵字: | cigarette smoke; elastase; heat shock protein 70; lentivirus vector; manganese superoxide dismutase; resveratrol; transcription factor Nrf2; vasculotropin A; heat shock protein 70; pancreatic elastase; resveratrol; smoke; stilbene derivative; vasculotropin A; VEGFA protein, human; animal cell; animal experiment; animal model; antioxidant responsive element; Article; bone marrow derived mesenchymal stem cell; cell survival; elastase-induced emphysema; female; jugular vein; lung function; mouse; mouse model; nonhuman; nonviral gene delivery system; nucleotide sequence; oxidative stress; priority journal; promoter region; protein expression; quantitative analysis; real time polymerase chain reaction; respiratory function; Western blotting; adverse effects; animal; C57BL mouse; cell culture; disease model; drug effects; emphysema; genetics; lung; mesenchymal stroma cell; metabolism; smoke; tobacco; Animals; Cell Survival; Cells, Cultured; Disease Models, Animal; Emphysema; Female; HSP70 Heat-Shock Proteins; Lung; Mesenchymal Stromal Cells; Mice; Mice, Inbred C57BL; Pancreatic Elastase; Smoke; Stilbenes; Tobacco; Vascular Endothelial Growth Factor A |
顯示於: | 醫學系 |
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