title: Therapeutic effect of human umbilical cord mesenchymal stem cells modified by angiotensin-converting enzyme 2 gene on bleomycin-induced lung fibrosis injury.
abstract: The aim of the present study was to evaluate the therapeutic effects of human umbilical cord mesenchymal stem cells (uMSCs) in the presence of angiotensin‑converting enzyme 2 gene (ACE2; ACE2‑uMSCs) on bleomycin (BLM)‑induced lung injury and pulmonary fibrosis in mice. A total of 100 male C57BL/6 mice were divided at random into five groups (n=20) as follows: Control group, BLM group, ACE2 group, uMSC group and ACE2‑uMSC group. At 7, 14 and 28 days post‑treatment, the following parameters were evaluated in lung tissue: Oxidation indexes [malondialedehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and oxidized glutathione (GSSG)]; fibrosis factors [tumor necrosis factor (TNF)‑α, interferon (IFN)‑γ and transforming growth factor (TGF)‑β]; inflammatory cytokines [Interleukin (IL)‑1, IL‑2, IL‑6 and IL‑10]; ACE2 gene expression; hydroxyproline and collagen type 1 messenger RNA (mRNA) concentration; as well as matrix metalloproteinase (MMPs; 2 and 9) and tissue inhibitor of metalloproteinase (TIMP)1‑4 expression. ACE2‑uMSC injection following bleomycin pretreatment significantly alleviated lung injury in mice. In addition, treatment with ACE2‑uMSCs demonstrated a stronger therapeutic effect than ACE2‑ or uMSC treatment alone, indicated by decreased expression of MDA, GSSG, TNF‑α, IFN‑γ, TGF‑β, IL‑1, IL‑2, IL‑6, collagen type 1 mRNA, MMPs and TIMPs as well as hydroxyproline concentration, and upregulation of SOD, GSH and ACE2 and IL‑10. In conclusion, the results of the present study demonstrated that ACE2 and uMSCs had a synergistic therapeutic effect on bleomycin‑induced acute lung injury.
authors.affiliation: Department of Obstetrics, First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Min
authors.affiliation: Department of Respiratory Medicine, Shanghai Jiangong Hospital, Shanghai 200083, P.R. China.
authors.forename: Fengying
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Pediatrics, First People's Hospital of Kunshan, Affiliated to Jiangsu University, Kunshan 215300, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, P.R. China.
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001761:Bleomycin / Q000009:adverse effects*; D002454:Cell Differentiation; D003094:Collagen / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology*; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D055370:Lung Injury / Q000209:etiology* / Q000473:pathology / Q000628:therapy*; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010641:Phenotype; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D000954:Antigens, Surface; D018836:Inflammation Mediators; D019714:Tissue Inhibitor of Metalloproteinases; D001761:Bleomycin; D003094:Collagen; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; D020782:Matrix Metalloproteinases