title: Pantethine Prevents Murine Systemic Sclerosis Through the Inhibition of Microparticle Shedding.
abstract: OBJECTIVE
  Endothelial cell (EC) damage in systemic sclerosis (SSc) is reflected by the shedding of microparticles (MPs). The aim of this study was to show that inhibiting MP release using pantethine or by inactivating ATP-binding cassette transporter A1 (ABCA1) ameliorates murine SSc.
  
  
  METHODS
  First, the effects of pantethine on MP shedding and on basal oxidative and nitrosative stresses in ECs and fibroblasts were determined in vitro. The effects of pantethine were then tested in vivo. SSc was induced in BALB/c mice by daily intradermal injection of HOCl. Mice were simultaneously treated daily with pantethine by oral gavage.
  
  
  RESULTS
  In vitro, pantethine inhibited MP shedding from tumor necrosis factor-stimulated ECs and abrogated MP-induced oxidative and nitrosative stresses in ECs and fibroblasts. Ex vivo, pantethine also restored redox homeostasis in fibroblasts from mice with SSc. In vivo, mice with SSc displayed skin and lung fibrosis associated with increased levels of circulating MPs and markers of oxidative and endothelial stress, which were normalized by administration of pantethine or inactivation of ABCA1.
  
  
  CONCLUSIONS
  Pantethine is a well-tolerated molecule that represents a potential treatment of human SSc.
authors.affiliation: Université Paris Descartes, Sorbonne Paris-Cité, Institut Cochin, INSERM U1016, and Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Niloufar
authors.initials: N
authors.lastname: Kavian
authors.affiliation: Université Paris Descartes, Sorbonne Paris-Cité, Institut Cochin, INSERM U1016, and Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Wioleta
authors.initials: W
authors.lastname: Marut
authors.affiliation: Université Paris Descartes, Sorbonne Paris-Cité, Institut Cochin, INSERM U1016, and Hôpital Cochin, AP-HP, Paris, France, and Hôpital Robert Debré, Reims, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Servettaz
authors.affiliation: Université Paris Descartes, Sorbonne Paris-Cité, Institut Cochin, INSERM U1016, and Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Nicco
authors.affiliation: Université Paris Descartes, Sorbonne Paris-Cité, Institut Cochin, INSERM U1016, and Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Chéreau
authors.affiliation: Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Lemaréchal
authors.affiliation: Université Montpellier 1 and Hôpital St. Eloi, Montpellier, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Guilpain
authors.affiliation: Université d'Aix Marseille, Centre d'Immunologie de Marseille-Luminy, INSERM U631, and CNRS UMR6102, Marseille, France.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Chimini
authors.affiliation: Université d'Aix Marseille, UM2, Centre d'Immunologie de Marseille-Luminy, INSERM U1104, and CNRS UMR7280, Marseille, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Galland
authors.affiliation: Université Paris Descartes, Sorbonne Paris-Cité, Institut Cochin, INSERM U1016, and Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Weill
authors.affiliation: Université d'Aix Marseille, UM2, Centre d'Immunologie de Marseille-Luminy, INSERM U1104, and CNRS UMR7280, Marseille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Naquet
authors.affiliation: Université Paris Descartes, Sorbonne Paris-Cité, Institut Cochin, INSERM U1016, and Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Batteux
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D055252:Cell-Derived Microparticles / Q000187:drug effects* / Q000473:pathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis / Q000187:drug effects; D006997:Hypochlorous Acid / Q000008:administration & dosage / Q000009:adverse effects; D066298:In Vitro Techniques; D007271:Injections, Intradermal; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects; D010204:Pantetheine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D012595:Scleroderma, Systemic / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D064286:ATP Binding Cassette Transporter 1; D001761:Bleomycin; D006997:Hypochlorous Acid; D010204:Pantetheine; C577833:Abca1 protein, mouse; C005425:pantethine