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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.
AuthorsEmilie Baye, Morgan Gallazzini, Marianne Delville, Christophe Legendre, Fabiola Terzi, Guillaume Canaud
JournalKidney international (Kidney Int) Vol. 90 Issue 5 Pg. 1037-1044 (11 2016) ISSN: 1523-1755 [Electronic] United States
PMID27528551 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
Chemical References
  • B7-1 Antigen
Topics
  • Animals
  • B7-1 Antigen (metabolism)
  • Glomerulosclerosis, Focal Segmental (metabolism)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Podocytes (metabolism)
  • Primary Cell Culture

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