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

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.

• Authors: Young-Bin Chen, Ying-Wei Lan, Lih-Geeng Chen, Tsung-Teng Huang, Kong-Bung Choo, Winston T K Cheng, Hsuan-Shu Lee, Kowit-Yu Chong
• Journal: Cell stress & chaperones (Cell Stress Chaperones) Vol. 20 Issue 6 Pg. 979-89 (Nov 2015) ISSN: 1466-1268 [Electronic] Netherlands
• PMID: 26243699 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HSP70 Heat-Shock Proteins
• Smoke
• Stilbenes
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Pancreatic Elastase
• Resveratrol

Topics

• Animals
• Cell Survival (drug effects)
• Cells, Cultured
• Disease Models, Animal
• Emphysema (drug therapy, metabolism)
• Female
• HSP70 Heat-Shock Proteins (genetics)
• Lung (drug effects, metabolism)
• Mesenchymal Stem Cells (drug effects, metabolism)
• Mice
• Mice, Inbred C57BL
• Pancreatic Elastase (pharmacology)
• Resveratrol
• Smoke (adverse effects)
• Stilbenes (pharmacology, therapeutic use)
• Tobacco (adverse effects)
• Vascular Endothelial Growth Factor A (genetics, metabolism)