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Adenovirus-mediated anti-sense ERK2 gene therapy inhibits tubular epithelial-mesenchymal transition and ameliorates renal allograft fibrosis.
- Source :
-
Transplant immunology [Transpl Immunol] 2011 Jul; Vol. 25 (1), pp. 34-41. Date of Electronic Publication: 2011 Apr 16. - Publication Year :
- 2011
-
Abstract
- Purpose: 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.<br />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.<br />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.<br />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.<br /> (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
CD4-Positive T-Lymphocytes enzymology
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes enzymology
CD8-Positive T-Lymphocytes immunology
Cell Line
Connective Tissue Growth Factor immunology
Connective Tissue Growth Factor pharmacology
Epithelial-Mesenchymal Transition genetics
Fibrosis
Graft Rejection enzymology
Graft Rejection genetics
Graft Rejection immunology
Kidney Tubules enzymology
Male
Rats
Rats, Inbred F344
Rats, Inbred Lew
Transplantation, Homologous
Adenoviridae
DNA, Antisense
Epithelial-Mesenchymal Transition immunology
Genetic Therapy
Graft Rejection therapy
Kidney Transplantation
Kidney Tubules immunology
Mitogen-Activated Protein Kinase 1
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5492
- Volume :
- 25
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Transplant immunology
- Publication Type :
- Academic Journal
- Accession number :
- 21530658
- Full Text :
- https://doi.org/10.1016/j.trim.2011.04.001