TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000366930
  • Gene Name:TGFB2
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:RT-PCR
  • mRNA Pathway:NA
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:MG132
  • Drug Method:down-regulated the gene expression

Disease basic infommation

  • Disease:renal interstitial fibrosis
  • Tissue:tissues

Other information

  • Title:Effects of proteasome inhibitors on rat renal fibrosis in vitro and in vivo
  • Journal:Nephrology
  • Published:2011
  • PubMed ID:21175982
  • Abstract:Aim:Transforming growth factor-β (TGF-β) is involved in renal tubulointerstitial fibrosis. Recently, the ubiquitin proteasome system was shown to participate in the TGF-β signalling pathway. The aim of this study was to examine the effects of proteasome inhibitors on TGF-β-induced transformation of renal fibroblasts and tubular epithelial cells in vitro and on unilateral ureteral obstruction (UUO) in vivo. Methods:Rat renal fibroblasts NRK-49F cells and tubular epithelial cells, NRK-52E, were treated with TGF-β in the presence or absence of a proteasome inhibitor, MG132 or lactacystin. Rats were subjected to UUO and received MG132 i.p. for 7 days. Results:In cultured renal cells, both MG132 and lactacystin inhibited TGF-β-induced α-smooth muscle actin (α-SMA) protein expression according to both western blotting and immunofluorescent study results. MG132 also suppressed TGF-β-induced mRNA expression of α-SMA and upregulation of Smad-response element reporter activity. However, MG132 did not inhibit TGF-β-induced phosphorylation and nuclear translocation of Smad2. In contrast, MG132 increased the protein level of Smad co-repressor SnoN, demonstrating that SnoN is one of the target molecules by which MG132 blocks the TGF-β signalling pathway. Although the proteasome inhibitor suppressed TGF-β-induced transformation of cultured fibroblasts and tubular epithelial cells, MG132 treatment did not ameliorate tubulointerstitial fibrosis in the rat UUO model. Conclusion:Proteasome inhibitors attenuate TGF-β signalling by blocking Smad signal transduction in vitro, but do not inhibit renal interstitial fibrosis in vivo.
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