December 2002
Volume 43, Issue 13
ARVO Annual Meeting Abstract  |   December 2002
Signal Transduction Pathways For The Expression Of Genes For Mmp And Timp Induced By Stretching Human Fetal Scleral Fibroblasts
Author Affiliations & Notes
  • W Cui
    Ophthalmology Doheny Eye Institute Los Angeles CA
  • MR Bryant
    Ophthalmology Doheny Eye Institute Los Angeles CA
  • PJ McDonnell
    Ophthalmology University of California Irvine CA
  • Footnotes
    Commercial Relationships   W. Cui, None; M.R. Bryant, None; P.J. McDonnell, None. Grant Identification: Supported by NIH grant EY03040 and by the Ahmanson Foundation.
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 2467. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      W Cui, MR Bryant, PJ McDonnell; Signal Transduction Pathways For The Expression Of Genes For Mmp And Timp Induced By Stretching Human Fetal Scleral Fibroblasts . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2467.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Abstract: : Purpose:We previously found that integrin subunits α2, α5 and ß1 mediate signal transduction for the expression of genes for MMP-1 and MMP-2 induced by stretching human fetal scleral fibroblasts (HFSF). The purpose of this study is to determine a second signal transduction pathway for the expression of genes for MMP-1, MMP-2, TIMP-1, and TIMP-2. Methods:Prior to stretching the cells in vitro, we selectively inhibited protein kinase C (PKC), protein kinase A (PKA), extracellular signal-regulated kinase (ERK), tyrosine kinase (TK); disrupted cytoskeletal elements (microfilament, microtubule, and intermediate filaments), blocked cellular membrane L-type voltage-sensitive calcium channels (VSCC) or mechanosensive cation channel (MSCC). Gene expression was measured with RT-PCR and Southern blot. Results:Inhibiting PKC, TK, or ERK decreased stretch-induced MMP-1 gene expression. Disrupting microfilaments or blocking MSCC also decreased MMP-1 gene expression. For MMP-2, disrupting intermediate filaments, inhibiting PKC, or blocking MSCC or VSC decreased stretch-induced gene expression. Inhibiting PKC, TK, or ERK, disrupting microfilaments or blocking VSCC inhibited stretch-induced TIMP-1 gene expression. For TIMP-2, only inhibiting PKC or ERK inhibited stretch-induced gene expression. Conclusion:Our results indicate that protein kinases, ion channels and the cytoskeleton are involved in the stretch-induced mechanotransduction of MMP and TIMP gene expression. Among the signaling molecules, PKC is the most active because it affects the signal transduction for MMP-1, MMP-2, TIMP-1 and TIMP-2. PKA and microtubules are not involved in the stretch-induced signal transduction for the measured MMPs and TIMPs.

Keywords: 481 myopia • 580 signal transduction • 417 gene/expression 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.