Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol alleviates elastase-induced emphysema in a mouse model

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• 作者：Young-Bin Chen ; Ying-Wei Lan ; Lih-Geeng Chen…
• 关键词：Stem cell ; based gene therapy ; Resveratrol ; Hsp70 promoter ; VEGFA ; Mouse model ; Emphysema
• 刊名：Cell Stress and Chaperones
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：20
• 期：6
• 页码：979-989
• 全文大小：1,571 KB
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• 作者单位：Young-Bin Chen (1)
  Ying-Wei Lan (2)
  Lih-Geeng Chen (6)
  Tsung-Teng Huang (3)
  Kong-Bung Choo (7)
  Winston T. K. Cheng (8)
  Hsuan-Shu Lee (1) (9)
  Kowit-Yu Chong (10) (2) (4) (5)
  
  1. Institute of Biotechnology, College of Bioresources and Agriculture, National Taiwan University, Taipei, Taiwan, Republic of China
  2. Graduate Institute of Biomedical Sciences, Division of Biotechnology, Chang Gung University, Tao-Yuan, Taiwan, Republic of China
  6. Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi, 600, Taiwan, Republic of China
  3. Center for Molecular and Clinical Immunology, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan, Republic of China
  7. Department of Preclinical Sciences, Faculty of Medicine and Health Sciences and Centre for Stem Cell Research, Universiti Tunku Abdul Rahman, Selangor, Malaysia
  8. Department of Animal Science and Biotechnology, Tunghai University, Taichung, Taiwan, Republic of China
  9. Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicne, Taipei, Taiwan, Republic of China
  10. Department of Family Medicine, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan, Republic of China
  4. Molecular Medicine Research Center, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan, Republic of China
  5. Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan, Republic of China
  
• 刊物主题：Biomedicine general; Cell Biology; Biochemistry, general; Immunology; Cancer Research; Neurosciences;
• 出版者：Springer Netherlands
• ISSN：1466-1268

文摘

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. Keywords Stem cell-based gene therapy Resveratrol Hsp70 promoter VEGFA Mouse model Emphysema