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Expression of matrix metalloproteinase-9 associated with ets-1 proto-oncogene in rat tubulointerstitial cells.
Naito, Takashi; Tanihata, Yoko; Nishimura, Hideki; Tanaka, Toshihisa; Higuchi, Chieko; Taguchi, Takashi; Sanaka, Tsutomu.
Afiliação
  • Naito T; Department of Medicine, Tokyo Women's Medical University Daini Hospital, Arakawaku, Tokyo, Japan. takashi020304@yahoo.co.jp
Nephrol Dial Transplant ; 20(11): 2333-48, 2005 Nov.
Article em En | MEDLINE | ID: mdl-16046515
ABSTRACT

BACKGROUND:

Ets-1 proto-oncogene exhibits multiple activities in the transcriptional regulation of numerous genes including metalloproteinase (MMP)-1, -3 and -9. MMPs play an important role in the remodelling of extracellular matrix in various renal diseases. However, the role of the Ets-1-MMP axis in advanced renal diseases is uncertain. In the present study, we investigated whether Ets-1 is involved in interleukin (IL)-1-mediated expression of MMPs in tubulointerstitial cells.

METHODS:

Rat renal fibroblasts (NRK-49F) and tubular epithelial cells (NRK-52E) were cultured and allocated to an IL-1beta-treated group (10 ng/ml), a platelet-derived growth factor (PDGF)-BB-treated group (25 ng/ml) and a control group. Protein and mRNA were extracted after 1, 6, 12 and 24 h of treatment. Parallel flasks were treated with 2 muM ets-1 antisense oligodeoxynucleotides (ODNs) before exposure to IL-1beta. The expression of Ets-1 protein was evaluated by western blotting. The activities of MMPs were evaluated by gelatin zymography. The expression of ets-1 and/or MMP-9 mRNA was evaluated semiquantitatively by real-time reverse transcription-polymerase chain reaction (RT-PCR).

RESULTS:

In NRK-49F cells, Ets-1 protein increased significantly by 6.8-fold at 6 h, and MMP-9 activity increased significantly by 9.9-fold at 12 h in the IL-1beta-treated group compared with controls. MMP-2 and -3 activities also increased significantly in the IL-1beta-treated group. In NRK-52E cells, Ets-1 protein was 3.1 times higher at 1 h, and the latent form of MMP-9 activity increased 3.4-fold at 6 h in the IL-1beta group compared with controls. However, MMP-2 or MMP-3 activities were not markedly altered by IL-1beta treatment compared with controls. When the cells were treated with ets-1 antisense ODNs before IL-1beta treatment, Ets-1 protein expression decreased at least 50%, and MMP-9 activity was clearly inhibited in both cells. We also confirmed that MMP-9 activity was upregulated on days 21 and 28 in renal cortex of rat crescentic glomerulonephritis.

CONCLUSIONS:

The Ets-1 transcriptional factor may participate in IL-1beta-mediated MMP-9 expression in tubulointerstitial cells.
Assuntos
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Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: RNA Mensageiro / Expressão Gênica / Metaloproteinase 9 da Matriz / Células Mesangiais / Proteína Proto-Oncogênica c-ets-1 / Túbulos Renais Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Revista: Nephrol Dial Transplant Assunto da revista: NEFROLOGIA / TRANSPLANTE Ano de publicação: 2005 Tipo de documento: Article País de afiliação: Japão
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Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: RNA Mensageiro / Expressão Gênica / Metaloproteinase 9 da Matriz / Células Mesangiais / Proteína Proto-Oncogênica c-ets-1 / Túbulos Renais Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Revista: Nephrol Dial Transplant Assunto da revista: NEFROLOGIA / TRANSPLANTE Ano de publicação: 2005 Tipo de documento: Article País de afiliação: Japão