title: Adenovirus-mediated anti-sense ERK2 gene therapy inhibits tubular epithelial-mesenchymal transition and ameliorates renal allograft fibrosis.
abstract: OBJECTIVE
  Epithelial-mesenchymal transition (EMT) plays an important role in progress of renal allograft fibrosis. The adenovirus-mediated anti-sense extracellular signal-regulated kinase 2 (Adanti-ERK2) gene therapy was used to block ERK signaling pathway, and its effect on EMT and renal allograft fibrosis both in vivo and in vitro was explored.
  
  
  METHODS
  We first generated an in vitro EMT model by connective tissue growth factor (CTGF) stimulation in a HK-2 cell culture system, and then applied Adanti-ERK2 gene therapy on it. The transition of epithelial marker (E-cadherin) to mesenchymal markers (α-SMA, Vimentin) and the cell mobility function alteration were monitored for the observation of EMT progress. In vivo, a rat renal transplant model with Fisher-Lewis combination was employed and the Adanti-ERK2 gene therapy was given. The tubular EMT changes and pathology of allograft fibrosis were examined.
  
  
  RESULTS
  In vitro, Adanti-ERK2 gene therapy inhibited CTGF-induced tubular EMT and attenuated the cell motility function induced by CTGF. In vivo, Adanti-ERK2 gene therapy attenuated tubular EMT, modulated the infiltration of macrophages and CD8(+), CD4(+)T lymphocytes, and ameliorated fibrosis effectively in the renal allografts 24weeks after transplantation.
  
  
  CONCLUSIONS
  Adanti-ERK2 gene therapy inhibits tubular EMT and attenuates renal allograft fibrosis. It is possible to develop promising molecular drug(s) in the future based on ERK signaling pathway.
authors.affiliation: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Ding
authors.forename: Zhishui
authors.initials: Z
authors.lastname: Chen
authors.forename: Xilin
authors.initials: X
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: Cai
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
authors.forename: Nianqiao
authors.initials: N
authors.lastname: Gong
mesh_terms: D000256:Adenoviridae; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D002460:Cell Line; D055513:Connective Tissue Growth Factor / Q000276:immunology / Q000494:pharmacology; D016373:DNA, Antisense; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000276:immunology*; D005355:Fibrosis; D015316:Genetic Therapy; D006084:Graft Rejection / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000201:enzymology / Q000276:immunology*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous
chemical_list: C526316:CCN2 protein, rat; D016373:DNA, Antisense; D055513:Connective Tissue Growth Factor; D019950:Mitogen-Activated Protein Kinase 1