title: Mesenchymal stem cell transplantation increases expression of vascular endothelial growth factor in papain-induced emphysematous lungs and inhibits apoptosis of lung cells.
abstract: 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.
authors.affiliation: 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
authors.forename: Guohua
authors.initials: G
authors.lastname: Zhen
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xue
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhao
authors.forename: Naibing
authors.initials: N
authors.lastname: Gu
authors.forename: Zhouping
authors.initials: Z
authors.lastname: Tang
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Xu
authors.forename: Zhenxiang
authors.initials: Z
authors.lastname: Zhang
mesh_terms: 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*
chemical_list: D019138:Antibodies, Blocking; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D010206:Papain