RGD Reference Report - Expression of matrix metalloproteinase-9 associated with ets-1 proto-oncogene in rat tubulointerstitial cells. - Rat Genome Database

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Expression of matrix metalloproteinase-9 associated with ets-1 proto-oncogene in rat tubulointerstitial cells.

Authors: Naito, T  Tanihata, Y  Nishimura, H  Tanaka, T  Higuchi, C  Taguchi, T  Sanaka, T 
Citation: Naito T, etal., Nephrol Dial Transplant. 2005 Nov;20(11):2333-48. Epub 2005 Jul 26.
RGD ID: 2313720
Pubmed: PMID:16046515   (View Abstract at PubMed)
DOI: DOI:10.1093/ndt/gfi013   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MMP9Humancrescentic glomerulonephritis  ISOMmp9 (Rattus norvegicus)protein:increased expression:renal cortex (rat)RGD 
Mmp9Ratcrescentic glomerulonephritis  IEP protein:increased expression:renal cortex (rat)RGD 
Mmp9Mousecrescentic glomerulonephritis  ISOMmp9 (Rattus norvegicus)protein:increased expression:renal cortex (rat)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Mmp2Ratcellular response to interleukin-1  IEP Il-1betaRGD 
Mmp3Ratcellular response to interleukin-1  IEP Il-1betaRGD 
Mmp9Ratcellular response to interleukin-1  IEP Il-1betaRGD 
Ets1Ratresponse to interleukin-1  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ets1  (ETS proto-oncogene 1, transcription factor)
Mmp2  (matrix metallopeptidase 2)
Mmp3  (matrix metallopeptidase 3)
Mmp9  (matrix metallopeptidase 9)

Genes (Mus musculus)
Mmp9  (matrix metallopeptidase 9)

Genes (Homo sapiens)
MMP9  (matrix metallopeptidase 9)


Additional Information