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Transpl Immunol. 2011 Jul;25(1):34-41. doi: 10.1016/j.trim.2011.04.001. Epub 2011 Apr 16.

Adenovirus-mediated anti-sense ERK2 gene therapy inhibits tubular epithelial-mesenchymal transition and ameliorates renal allograft fibrosis.

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1
Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

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.

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.

PMID:
21530658
DOI:
10.1016/j.trim.2011.04.001
[Indexed for MEDLINE]
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