Albumin Is Recycled From the Primary Urine by Tubular Transcytosis

J Am Soc Nephrol. 2013 Dec;24(12):1966-80. doi: 10.1681/ASN.2013010018. Epub 2013 Aug 22.

Abstract

Under physiologic conditions, significant amounts of plasma protein pass the renal filter and are reabsorbed by proximal tubular cells, but it is not clear whether the endocytosed protein, particularly albumin, is degraded in lysosomes or returned to the circulatory system intact. To resolve this question, a transgenic mouse with podocyte-specific expression of doxycycline-inducible tagged murine albumin was developed. To assess potential glomerular backfiltration, two types of albumin with different charges were expressed. On administration of doxycycline, podocytes expressed either of the two types of transgenic albumin, which were secreted into the primary filtrate and reabsorbed by proximal tubular cells, resulting in serum accumulation. Renal transplantation experiments confirmed that extrarenal transcription of transgenic albumin was unlikely to account for these results. Genetic deletion of the neonatal Fc receptor (FcRn), which rescues albumin and IgG from lysosomal degradation, abolished transcytosis of both types of transgenic albumin and IgG in proximal tubular cells. In summary, we provide evidence of a transcytosis within the kidney tubular system that protects albumin and IgG from lysosomal degradation, allowing these proteins to be recycled intact.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / metabolism*
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Doxycycline / pharmacology
  • Endocytosis / physiology
  • Gene Expression / drug effects
  • Humans
  • Immunoglobulin G / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Kidney Transplantation
  • Kidney Tubules, Proximal / metabolism*
  • Lysosomes / metabolism
  • Membrane Proteins / genetics
  • Mice
  • Mice, Transgenic
  • Models, Biological*
  • Podocytes / metabolism
  • Protein Structure, Tertiary
  • Rats
  • Rats, Transgenic
  • Serum Albumin / chemistry
  • Serum Albumin / genetics
  • Serum Albumin / metabolism*
  • Transcytosis / physiology*

Substances

  • Anti-Bacterial Agents
  • Immunoglobulin G
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NPHS2 protein
  • Serum Albumin
  • Doxycycline