RGD Reference Report - Mycophenolic acid inhibits the autocrine PDGF-B synthesis and PDGF-BB-induced mRNA expression of Egr-1 in rat mesangial cells. - Rat Genome Database

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Mycophenolic acid inhibits the autocrine PDGF-B synthesis and PDGF-BB-induced mRNA expression of Egr-1 in rat mesangial cells.

Authors: Sabuda-Widemann, D  Grabensee, B  Schwandt, C  Blume, C 
Citation: Sabuda-Widemann D, etal., Nephrol Dial Transplant. 2009 Jan;24(1):52-61. doi: 10.1093/ndt/gfn462. Epub 2008 Aug 22.
RGD ID: 8553351
Pubmed: PMID:18723570   (View Abstract at PubMed)
DOI: DOI:10.1093/ndt/gfn462   (Journal Full-text)

BACKGROUND: Uncontrolled mesangial cell (MC) proliferation within the context of glomerular disease contributes to the development of glomerulosclerosis. Mesangial autocrine growth factor stimulation has been described as a pathogenic factor. We investigated the effects of mycophenolic acid (MPA), the active metabolite of the immunosuppressant mycophenolate mofetil (MMF), on proliferation factors of cultured rat MCs. MPA was tested on the expression of platelet-derived growth factor-B (PDGF-B) and its receptor beta (PDGFR-beta), the immediate early gene (IEG) c-fos and the early growth response gene-1 (Egr-1), and AP-1 activation. METHODS: Growth-arrested rat MCs were stimulated with 10% fetal calf serum (FCS) or 10-25 ng/ml platelet-derived growth factor-BB (PDGF-BB) in the presence or absence of MPA (0.019-10 microM) with or without guanosine (100 microM). MC proliferation was quantified by 5-bromo-2'-deoxyuridine (BrdU) incorporation and direct cell counting. Cytotoxicity of MPA was evaluated using the MTT and LDH tests. Protein expression of PDGF-B and its receptor PDGFR-beta was quantified by western blot analysis. The effect of MPA on gene expression of PDGF-B, Egr-1 and c-fos was determined by the reverse transcriptase-polymerase chain reaction (RT-PCR). AP-1 activation was analysed by an electrophoretic mobility shift assay (EMSA). RESULTS: Exposure of MCs to MPA caused a concentration-dependent inhibition of FCS-induced cell proliferation (cell number increase) with an IC50 of 0.44 +/- 0.03 microM and DNA synthesis with an IC50 of 0.52 +/- 0.02 microM without cell cytotoxicity in the therapeutic range. MPA decreased the PDGF-B protein expression and mRNA self-induction of PDGF-B but did not alter the protein expression of PDGFR-beta. MPA strongly inhibited the PDGF-BB-induced mRNA expression of Egr-1 decreasing to 7.6 +/- 2.5% after 30 min (P



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Egr1Ratcellular response to mycophenolic acid involved_inIDA PMID:18723570UniProt 
PdgfbRatcellular response to mycophenolic acid involved_inIDA PMID:18723570UniProt 
Egr1Ratglomerular mesangial cell proliferation involved_inIMP PMID:18723570UniProt 
PdgfbRatpositive regulation of DNA-templated transcription involved_inIDA PMID:18723570UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Egr1  (early growth response 1)
Pdgfb  (platelet derived growth factor subunit B)


Additional Information