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Slit2-Robo Signaling Promotes Glomerular Vascularization and Nephron Development.
Li, Jinyu; Geraldo, Luiz Henrique; Dubrac, Alexandre; Zarkada, Georgia; Eichmann, Anne.
Afiliação
  • Li J; Department of Cellular and Molecular Physiology, Yale University Medical School, New Haven, Connecticut.
  • Geraldo LH; Cardiovascular Research Center, Department of Internal Medicine, Yale University, New Haven, Connecticut.
  • Dubrac A; Cardiovascular Research Center, Department of Internal Medicine, Yale University, New Haven, Connecticut.
  • Zarkada G; Université de Paris, Paris Cardiovascular Research Center, Institut National de la Santé et de la Recherche Médicale U907, Paris, France.
  • Eichmann A; Cardiovascular Research Center, Department of Internal Medicine, Yale University, New Haven, Connecticut.
J Am Soc Nephrol ; 32(9): 2255-2272, 2021 09.
Article em En | MEDLINE | ID: mdl-34341180
BACKGROUND: Kidney function requires continuous blood filtration by glomerular capillaries. Disruption of glomerular vascular development or maintenance contributes to the pathogenesis of kidney diseases, but the signaling events regulating renal endothelium development remain incompletely understood. Here, we discovered a novel role of Slit2-Robo signaling in glomerular vascularization. Slit2 is a secreted polypeptide that binds to transmembrane Robo receptors and regulates axon guidance as well as ureteric bud branching and angiogenesis. METHODS: We performed Slit2-alkaline phosphatase binding to kidney cryosections from mice with or without tamoxifen-inducible Slit2 or Robo1 and -2 deletions, and we characterized the phenotypes using immunohistochemistry, electron microscopy, and functional intravenous dye perfusion analysis. RESULTS: Only the glomerular endothelium, but no other renal endothelial compartment, responded to Slit2 in the developing kidney vasculature. Induced Slit2 gene deletion or Slit2 ligand trap at birth affected nephrogenesis and inhibited vascularization of developing glomeruli by reducing endothelial proliferation and migration, leading to defective cortical glomerular perfusion and abnormal podocyte differentiation. Global and endothelial-specific Robo deletion showed that both endothelial and epithelial Robo receptors contributed to glomerular vascularization. CONCLUSIONS: Our study provides new insights into the signaling pathways involved in glomerular vascular development and identifies Slit2 as a potential tool to enhance glomerular angiogenesis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores Imunológicos / Peptídeos e Proteínas de Sinalização Intercelular / Glomérulos Renais / Néfrons / Proteínas do Tecido Nervoso Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Am Soc Nephrol Assunto da revista: NEFROLOGIA Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores Imunológicos / Peptídeos e Proteínas de Sinalização Intercelular / Glomérulos Renais / Néfrons / Proteínas do Tecido Nervoso Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Am Soc Nephrol Assunto da revista: NEFROLOGIA Ano de publicação: 2021 Tipo de documento: Article