title: Shedding of dipeptidyl peptidase 4 is mediated by metalloproteases and up-regulated by hypoxia in human adipocytes and smooth muscle cells.
abstract: 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.
authors.affiliation: Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Röhrborn
authors.affiliation: Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Eckel
authors.affiliation: Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany. Electronic address: henrike.sell@ddz.uni-duesseldorf.de.
authors.forename: Henrike
authors.initials: H
authors.lastname: Sell
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020126:Brefeldin A / Q000494:pharmacology; D015687:Cell Hypoxia; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D012995:Solubility; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D011480:Protease Inhibitors; D020126:Brefeldin A; D018819:Dipeptidyl Peptidase 4; D020782:Matrix Metalloproteinases
keywords: CD26/DPP4; Hypoxia; Non-classical secretion; Protease