title: Effects of oxygen tension and dextran-shelled/2H,3H-decafluoropentane-cored oxygen-loaded nanodroplets on secretion of gelatinases and their inhibitors in term human placenta.
abstract: Matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) need to be finely modulated in physiological processes. However, oxygen tension influences MMP/TIMP balances, potentially leading to pathology. Intriguingly, new 2H,3H-decafluoropentane-based oxygen-loaded nanodroplets (OLNDs) have proven effective in abrogating hypoxia-dependent dysregulation of MMP and TIMP secretion by single cell populations. This work explored the effects of different oxygen tensions and dextran-shelled OLNDs on MMP/TIMP production in an organized and multicellular tissue (term human placenta). Chorionic villous explants from normal third-trimester pregnancies were incubated with/without OLNDs in 3 or 20% O2. Explants cultured at higher oxygen tension released constitutive proMMP-2, proMMP-9, TIMP-1, and TIMP-2. Hypoxia significantly altered MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios enhancing TIMP-2 and reducing proMMP-2, proMMP-9, and TIMP-1 levels. Intriguingly, OLNDs effectively counteracted the effects of low oxygen tension. Collectively, these data support OLND potential as innovative, nonconventional, and cost-effective tools to counteract hypoxia-dependent dysregulation of MMP/TIMP balances in human tissues.
authors.affiliation: a Dipartimento di Neuroscienze , Università di Torino , Torino , Italy.|b Dipartimento di Scienze della Sanità Pubblica e Pediatriche , Università di Torino , Torino , Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Prato
authors.affiliation: a Dipartimento di Neuroscienze , Università di Torino , Torino , Italy.
authors.forename: Amina
authors.initials: A
authors.lastname: Khadjavi
authors.affiliation: c Istituto Nazionale di Ricerca Metrologica (INRIM) , Torino , Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Magnetto
authors.affiliation: d Dipartimento di Oncologia , Università di Torino , Torino , Italy.
authors.forename: Giulia Rossana
authors.initials: GR
authors.lastname: Gulino
authors.affiliation: e Dipartimento di Scienze Chirurgiche , Università di Torino , Torino , Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rolfo
authors.affiliation: e Dipartimento di Scienze Chirurgiche , Università di Torino , Torino , Italy.
authors.forename: Tullia
authors.initials: T
authors.lastname: Todros
authors.affiliation: f Dipartimento di Scienza e Tecnologia del Farmaco , Università di Torino , Torino , Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Cavalli
authors.affiliation: a Dipartimento di Neuroscienze , Università di Torino , Torino , Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Guiot
mesh_terms: D003911:Dextrans / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005466:Fluorocarbons / Q000737:chemistry*; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D049329:Nanostructures; D010100:Oxygen / Q000737:chemistry*; D010920:Placenta / Q000201:enzymology* / Q000378:metabolism; D011247:Pregnancy
chemical_list: D003911:Dextrans; D004791:Enzyme Inhibitors; D005466:Fluorocarbons; D018093:Gelatinases; C000605796:2H,3H-decafluoropentane; D010100:Oxygen
keywords: human placenta; matrix metalloproteinase (MMP); nanodroplet; oxygen; tissue inhibitor of metalloproteinase (TIMP)