Matrix metalloproteinase 9 expression: new regulatory elements

  • Irina Surgucheva
  • Kumaravel Chidambaram
  • David A. Willoughby
  • Andrei Surguchov
Article

Abstract

Retinal ganglion cells apoptosis is linked to matrix metalloproteinase 9 (MMP-9) controlled changes of extracellular matrix. Abnormal expression of MMP-9 is associated with glaucomatous alterations. Thus, the knowledge of MMP-9 regulation is important for the understanding the pathogenesis of glaucoma. Here, we investigated the role of 3′-untranslated regions (3′-UTR) and microRNAs in MMP-9 regulation. We used in vitro mutagenesis and Luc reporter system to identify regulatory elements in the 3′-UTR of MMP-9. microRNAs were analyzed by qRT-PCR, and their role was investigated with inhibitors and mimics. We identified targets for miRNAs in 3′-UTR of MMP-9 involved in the regulation of MMP-9 expression. We then isolated miRNAs from the optic nerve A7 astrocytes and 293 T cells and confirmed the role of mi340 in the regulation using specific inhibitors and mimics. The results obtained show a new miRNA-mediated mechanism of MMP-9 expression regulation.

Keywords

Retinal ganglion cells Matrix metalloproteinases Extracellular matrix MicroRNA Untranslated region 

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Copyright information

© US Government 2010

Authors and Affiliations

  • Irina Surgucheva
    • 1
    • 2
  • Kumaravel Chidambaram
    • 3
  • David A. Willoughby
    • 3
  • Andrei Surguchov
    • 1
    • 2
  1. 1.Laboratory of Retinal BiologyVA Medical CenterKansas CityUSA
  2. 2.Department of NeurologyKansas University Medical CenterKansas CityUSA
  3. 3.Ocean Ridge BiosciencesPalm Beach GardensUSA

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