TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000315274
  • Gene Name:MMP1
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:NA
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB01782
  • Drug Name:Pyrazolanthrone
  • Drug Method:down-regulated the gene expression

Disease basic infommation

  • Disease:tissue fibrosis
  • Tissue:tissues

Other information

  • Title:Caveolin-1 is a negative regulator of MMP-1 gene expression in human dermal fibroblasts via inhibition of Erk1/2/Ets1 signaling pathway
  • Journal:Journal of Dermatological Science
  • Published:2011
  • PubMed ID:21925842
  • Abstract:Background:Caveolar raft domains, also termed caveolae, are flask shaped invaginations that require the expression of the structural protein caveolin-1 (cav-1). Matrix metalloproteinase 1 (MMP-1) is a collagenase capable of degrading insoluble triple helical collagens. Deregulation of MMP-1 contributes to various pathological processes, including tissue fibrosis and impaired wound healing. Objective:In this study we investigated the role of cav-1 in MMP-1 gene regulation in human dermal fibroblasts. Methods:Fibroblasts were isolated from healthy subjects. Western blot was used to analyze protein levels and quantitative real time RT-PCR was used to measure mRNA expression. Cells were transiently transfected with siRNA oligos against acid sphingomyelinase (ASMase) and cav-1, or transduced with adenoviruses overexpressing ASMase and cav-1. The specific pharmacological inhibitors UO126 and SP600125 were used to block Erk1/2 and JNK activity. Results:This study shows that siRNA-mediated depletion of ASMase or cav-1, results in upregulation of MMP-1 gene expression. Similarly, MMP-1 expression was decreased after overexpresssion of cav-1 via an adenoviral vector. Depletion of cav-1 had no effect on JNK phosphorylation, while it resulted in an increase in Erk1/2 and Ets1 phosphorylation levels. Furthermore, in cav-1 depleted cells treated with the Erk inhibitor UO126, there was no increase in the levels of phospho-Erk1/2, phospho-Ets1, and MMP-1, suggesting that cav-1 mediated effects on MMP-1 and phospho-Ets1 are Erk1/2 dependent. Conclusions:In conclusion, this study has revealed an important role for cav-1 as a negative regulator of MMP-1 gene expression via inhibition of Erk1/2/Ets1 signaling. Cav-1 could potentially be a therapeutic target in diseases with deregulated extracellular matrix (ECM) turnover.
@Copyright Harbin Medical University
　The 2nd Affiliated Hospital of Harbin Medical University
　 备案号：鲁ICP备2022025566号-3