title: The costimulatory receptor B7-1 is not induced in injured podocytes.
abstract: Recent research on podocytes has proposed B7-1 as an important player in podocyte biology and as a potential new therapeutic target. B7-1 was upregulated in injured podocytes and described as a biomarker to identify patients who may benefit from abatacept, a B7-1 blocker. However, after this initial enthusiasm, several reports have not confirmed the efficiency of abatacept at inducing proteinuria remission in patients. In order to resolve these discrepancies, we explored the role of B7-1 in the injured podocyte. Both primary cultured and immortalized podocytes were exposed to lipopolysaccharides, but this failed to induce B7-1 expression at the mRNA and protein levels. Importantly, TLR-4 engagement confirmed lipopolysaccharide efficacy. We then evaluated B7-1 expression in several mouse models of podocyte injury including treatment with lipopolysaccharide or Adriamycin, a lupus prone model (NZB/W F1) and subtotal nephrectomy. Using 3 commercially available anti-B7-1 antibodies and appropriate controls, we could not find B7-1 expression in podocytes, whereas some infiltrating cells were positive. Thus, our findings do not support a role for B7-1 in podocyte biology. Hence, further studies are mandatory before treating proteinuric patients with B7-1 blockers.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1151, Institut Necker Enfants Malades, Hôpital Necker-Enfants Malades, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Baye
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1151, Institut Necker Enfants Malades, Hôpital Necker-Enfants Malades, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Morgan
authors.initials: M
authors.lastname: Gallazzini
authors.affiliation: Service de Néphrologie Transplantation Adultes, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Delville
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1151, Institut Necker Enfants Malades, Hôpital Necker-Enfants Malades, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Service de Néphrologie Transplantation Adultes, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1151, Institut Necker Enfants Malades, Hôpital Necker-Enfants Malades, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Terzi
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1151, Institut Necker Enfants Malades, Hôpital Necker-Enfants Malades, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Service de Néphrologie Transplantation Adultes, Hôpital Necker-Enfants Malades, Paris, France. Electronic address: guillaume.canaud@inserm.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Canaud
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism*; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050199:Podocytes / Q000378:metabolism*; D061251:Primary Cell Culture
chemical_list: D018122:B7-1 Antigen
keywords: B7-1; albuminuria; cytoskeleton; podocytes