2. Academic Validation
  3. Pantethine Prevents Murine Systemic Sclerosis Through the Inhibition of Microparticle Shedding

Pantethine Prevents Murine Systemic Sclerosis Through the Inhibition of Microparticle Shedding

  • Arthritis Rheumatol. 2015 Jul;67(7):1881-90. doi: 10.1002/art.39121.
Niloufar Kavian 1,  Wioleta Marut 1,  Amélie Servettaz 2,  Carole Nicco 1,  Christiane Chéreau 1,  Hervé Lemaréchal 3,  Philippe Guilpain 4,  Giovanna Chimini 5,  Franck Galland 6,  Bernard Weill 1,  Philippe Naquet 6,  Frédéric Batteux 1
Affiliations

Affiliations

  • 1 Université Paris Descartes, Sorbonne Paris-Cité, Institut Cochin, INSERM U1016, and Hôpital Cochin, AP-HP, Paris, France.
  • 2 Université Paris Descartes, Sorbonne Paris-Cité, Institut Cochin, INSERM U1016, and Hôpital Cochin, AP-HP, Paris, France, and Hôpital Robert Debré, Reims, France.
  • 3 Hôpital Cochin, AP-HP, Paris, France.
  • 4 Université Montpellier 1 and Hôpital St. Eloi, Montpellier, France.
  • 5 Université d'Aix Marseille, Centre d'Immunologie de Marseille-Luminy, INSERM U631, and CNRS UMR6102, Marseille, France.
  • 6 Université d'Aix Marseille, UM2, Centre d'Immunologie de Marseille-Luminy, INSERM U1104, and CNRS UMR7280, Marseille, France.
PMID: 25776044 DOI: 10.1002/art.39121
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.

Conclusion: Pantethine is a well-tolerated molecule that represents a potential treatment of human SSc.

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