Mesenchymal stem cell transplantation increases expression of vascular endothelial growth factor in papain-induced emphysematous lungs and inhibits apoptosis of lung cells.
BACKGROUND
Pulmonary emphysema is characterized by loss of alveolar structures. We have found that bone marrow (BM) mesenchymal stem cell (MSC) transplantation ameliorates papain-induced pulmonary emphysema. However, the underlying mechanism is not completely understood. It has been shown that blocking the vascular endothelial growth factor (VEGF) signaling pathway leads to apoptosis of lung cells and pulmonary emphysema, and MSC are capable of secreting VEGF. We hypothesized that MSC transplantation may have a protective effect on pulmonary emphysema by increasing VEGF-A expression and inhibiting apoptosis of lung cells.


METHODS
We examined the morphology and expression of VEGF-A in rat lung after papain treatment and MSC transplantation. We also used a co-culture system in which MSC and cells prepared from papain-treated lungs or control lungs were cultured together. The levels of VEGF-A in cells and culture medium were determined, and apoptosis of cultured lung cells was evaluated.


RESULTS
VEGF-A expression in rat lungs was decreased after papain treatment, which was partly rescued by MSC transplantation. MSC production of VEGF-A was increased when MSC were co-cultured with cells prepared from papain-treated lungs. Furthermore, the apoptosis of papain-treated lung cells was inhibited when co-cultured with MSC. The induction of MSC production of VEGF-A by papain-treated lung cells was inhibited by adding anti-tumor necrosis factor (TNF)-alpha antibody to the medium.


CONCLUSIONS
The protective effect of MSC transplantation on pulmonary emphysema may be partly mediated by increasing VEGF-A expression and inhibiting the apoptosis of lung cells. TNF-alpha released from papain-treated lung cells induces MSC to secret VEGF-A.
Zhen
Guohua
G
Division of Respiratory Diseases, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. ghzhen@tjh.tjmu.edu.cn
Xue
Zheng
Z
Zhao
Jianping
J
Gu
Naibing
N
Tang
Zhouping
Z
Xu
Yongjian
Y
Zhang
Zhenxiang
Z
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D017209:Apoptosis; D001853:Bone Marrow / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010206:Papain / Q000008:administration & dosage; D029424:Pulmonary Disease, Chronic Obstructive / Q000628:therapy; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D019138:Antibodies, Blocking; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D010206:Papain