GFOGER Peptide Modifies the Protein Content of Extracellular Vesicles and Inhibits Vascular Calcification

Autor: Mansour, Ali, Darwiche, Walaa, Yaker, Linda, da Nascimento, Sophie, Gomila, Cathy, Rossi, Claire, Jung, Vincent, Sonnet, Pascal, Kamel, Saïd, Guerrera, Ida, Boullier, Agnès, Ausseil, Jérôme
Přispěvatelé: Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Génie Enzymatique et Cellulaire (GEC), Université de Technologie de Compiègne (UTC)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Université de Technologie de Compiègne (UTC), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Octave, Stephane, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Frontiers in Cell and Developmental Biology
Frontiers in Cell and Developmental Biology, Frontiers media, 2020, 8, pp.589761. ⟨10.3389/fcell.2020.589761⟩
Frontiers in Cell and Developmental Biology, 2020, 8, pp.589761. ⟨10.3389/fcell.2020.589761⟩
ISSN: 2296-634X
DOI: 10.3389/fcell.2020.589761⟩
Popis: International audience; Objective Vascular calcification (VC) is an active process during which vascular smooth muscle cells (VSMCs) undergo an osteogenic switch and release extracellular vesicles (EVs). In turn, the EVs serve as calcification foci via interaction with type 1 collagen (COL1). We recently showed that a specific, six-amino-acid repeat (GFOGER) in the sequence of COL1 was involved in the latter’s interaction with integrins expressed on EVs. Our main objective was to test the GFOGER ability to inhibit VC.Approach We synthesized the GFOGER peptide and tested its ability to inhibit the inorganic phosphate (Pi)-induced calcification of VSMCs and aortic rings. Using mass spectrometry, we studied GFOGER’s effect on the protein composition of EVs released from Pi-treated VSMCs.Results Calcification of mouse VSMCs (MOVAS-1 cells), primary human VSMCs, and rat aortic rings was lower in the presence of GFOGER than with Pi alone (with relative decreases of 66, 58, and 91%, respectively; p < 0.001 for all) (no effect was observed with the scramble peptide GOERFG). A comparative proteomic analysis of EVs released from MOVAS-1 cells in the presence or absence of Pi highlighted significant differences in EVs’ protein content. Interestingly, the expression of some of the EVs’ proteins involved in the calcification process (such as osteogenic markers, TANK-binding kinase 1, and casein kinase II) was diminished in the presence of GFOGER peptide (data are available via ProteomeXchange with identifier PXD018169 ∗ ). The decrease of osteogenic marker expression observed in the presence of GFOGER was confirmed by q-RT-PCR analysis.Conclusion GFOGER peptide reduces vascular calcification by modifying the protein content of the subsequently released EVs, in particular by decreasing osteogenicswitching in VSMCs.
Databáze: OpenAIRE
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