Kathrin Weyer

Abolishment of proximal tubule albumin endocytosis does not affect plasma albumin during nephrotic syndrome in mice

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Kathrin Weyer
  • Pia K Andersen
  • ,
  • Kasper Schmidt, Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  • ,
  • Geraldine Mollet, Inserm U1163, Imagine Institute, Laboratory of Hereditary Kidney Diseases, Paris, France; Paris Descartes-Sorbonne Paris Cité University, Paris, France.
  • ,
  • Corinne Antignac, Inserm U1163, Imagine Institute, Laboratory of Hereditary Kidney Diseases, Paris, France; Paris Descartes-Sorbonne Paris Cité University, Paris, France; Department of Genetics, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • ,
  • Henrik Birn
  • Rikke Nielsen
  • Erik I Christensen

The megalin/cubilin receptor complex is required for proximal tubular endocytosis and degradation of filtered albumin. An additional high-capacity retrieval pathway of intact albumin for the recovery of large amounts of filtered albumin has been proposed, possibly involving cooperation between megalin/cubilin and the neonatal Fc receptor. To clarify the potential role of such a pathway, we examined the effects of megalin/cubilin gene inactivation on tubular albumin uptake and plasma albumin levels in nephrotic, podocin knockout mice. Immunofluorescence microscopy of megalin/cubilin/podocin knockout mouse kidneys demonstrated abolishment of proximal tubule albumin uptake, in contrast to the excessive albumin accumulation observed in podocin knockout mice compared to controls. Correspondingly, urinary albumin excretion was increased 1.4 fold in megalin/cubilin/podocin compared to podocin knockout mice (albumin/creatinine: 226 vs. 157 mg/mg). However, no difference in plasma albumin levels was observed between megalin/cubilin/podocin and podocin knockout mice, as both were reduced to approximately 40% of controls. There were no differences in liver albumin synthesis by mRNA levels and protein abundance. Thus, megalin/cubilin knockout efficiently blocks proximal tubular albumin uptake in nephrotic mice but plasma albumin levels did not differ as a result of megalin/cubilin-deficiency, suggesting no significance of the megalin/cubilin-pathway for albumin homeostasis by retrieval of intact albumin.

Original languageEnglish
JournalKidney International
Volume93
Issue2
Pages (from-to)335-342
Number of pages8
ISSN0085-2538
DOIs
Publication statusPublished - 1 Feb 2018

    Research areas

  • albuminuria, endocytosis, nephrotic syndrome, proteinuria, proximal tubule

See relations at Aarhus University Citationformats

ID: 118217629