Metalloproteinase Activators Of Notch Signaling In Development And Pancreatic Disease.

Overview

Notch signaling is involved in numerous cell-signaling events, both during development and disease. We used an in vitro model of pancreatic disease to examine metalloproteinase influences on Notch activity. Acinar-to-ductal metaplasia in the pancreas is associated with an increased risk for tumorigenesis. Examination of this process in vitro has shown that primary acinar cells, in response to EGF receptor ligands, can transdifferentiate into duct-like epithelia, in a Notch pathway-dependent manner. Matrix ...
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Overview

Notch signaling is involved in numerous cell-signaling events, both during development and disease. We used an in vitro model of pancreatic disease to examine metalloproteinase influences on Notch activity. Acinar-to-ductal metaplasia in the pancreas is associated with an increased risk for tumorigenesis. Examination of this process in vitro has shown that primary acinar cells, in response to EGF receptor ligands, can transdifferentiate into duct-like epithelia, in a Notch pathway-dependent manner. Matrix Metalloproteinase 7 (MMP-7) is a proteinase expressed in most metaplastic epithelia in vivo. Here, we show that in vitro acinar transdifferentiation is mediated by MMP-7?s ability to activate Notch. Besides being necessary for acinar transdifferentiation, it was found that MMP-7 activity was sufficient to induce the process, indicating that molecular signals capable of initiating MMP-7 expression also have the potential to induce formation of metaplastic epithelia in the pancreas. A Disintegrin and Metalloproteinase 10 (ADAM-10) has been shown to be required for Notch activity, however it is unclear where along the Notch pathway ADAM-10 functions. Here, we introduce a conditional ADAM-10 knockout mouse to further dissect its role in Notch signaling. We found that ADAM-10 activity is essential for the extracellular processing of Notch, but not for the intracellular processing necessary for proper Notch maturation. We also identified various phenotypes associated with defective Notch signaling in the embryo, skin and brain of the knockout mouse.
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Product Details

  • ISBN-13: 9781243564757
  • Publisher: BiblioLabsII
  • Publication date: 9/3/2011
  • Pages: 78
  • Product dimensions: 7.44 (w) x 9.69 (h) x 0.16 (d)

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