Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol alleviates elastase-induced emphysema in a mouse model
Journal
Cell Stress and Chaperones
Journal Volume
20
Journal Issue
6
Pages
979-989
Date Issued
2015
Author(s)
Abstract
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.
Subjects
Emphysema; Hsp70 promoter; Mouse model; Resveratrol; Stem cell-based gene therapy; VEGFA
SDGs
Other Subjects
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
Publisher
Cell Stress and Chaperones
Type
journal article