4.5 Article

Shedding of dipeptidyl peptidase 4 is mediated by metalloproteases and up-regulated by hypoxia in human adipocytes and smooth muscle cells

Journal

FEBS LETTERS
Volume 588, Issue 21, Pages 3870-3877

Publisher

WILEY
DOI: 10.1016/j.febslet.2014.08.029

Keywords

CD26/DPP4; Hypoxia Non-classical secretion; Protease

Funding

  1. Ministry of Science and Research of the State of North Rhine-Westphalia (MIWF NRW)
  2. Federal Ministry of Health (BMG)
  3. Deutsche Forschungsgemeinschaft [SE-1922 2-2]
  4. German Diabetes Association (DDG)
  5. European Foundation for the Study of Diabetes (EFSD)

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Dipeptidyl peptidase 4 is an important drug target for diabetes and a novel adipokine. However, it is unknown how soluble DPP4 (sDPP4) is cleaved from the cell membrane and released into the circulation. We show here that MMP1, MMP2 and MMP14 are involved in DPP4 shedding from human vascular smooth muscle cells (SMC) and MMP9 from adipocytes. Hypoxia increased DPP4 shedding from SMC which is associated with increased mRNA expression of MMP1. Our data suggest that constitutive as well as hypoxia-induced DPP4 shedding occurs due to a complex interplay between different MMPs in cell type-specific manner. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

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