title: Albumin is recycled from the primary urine by tubular transcytosis.
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.
authors: Divisions of Nephrology and Immunology and.
authors: Verena
authors: V
authors: Tenten
authors: Sylvia
authors: S
authors: Menzel
authors: Uta
authors: U
authors: Kunter
authors: Eva-Maria
authors: EM
authors: Sicking
authors: Claudia R C
authors: CR
authors: van Roeyen
authors: Silja K
authors: SK
authors: Sanden
authors: Michaela
authors: M
authors: Kaldenbach
authors: Peter
authors: P
authors: Boor
authors: Astrid
authors: A
authors: Fuss
authors: Sandra
authors: S
authors: Uhlig
authors: Regina
authors: R
authors: Lanzmich
authors: Brigith
authors: B
authors: Willemsen
authors: Henry
authors: H
authors: Dijkman
authors: Martin
authors: M
authors: Grepl
authors: Klemens
authors: K
authors: Wild
authors: Wilhelm
authors: W
authors: Kriz
authors: Bart
authors: B
authors: Smeets
authors: Jürgen
authors: J
authors: Floege
authors: Marcus J
authors: MJ
authors: Moeller
mesh_terms: D000419:Albuminuria / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004318:Doxycycline / Q000494:pharmacology; D004705:Endocytosis / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D016030:Kidney Transplantation; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D050199:Podocytes / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D055647:Rats, Transgenic; D012709:Serum Albumin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057900:Transcytosis / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D007074:Immunoglobulin G; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D012709:Serum Albumin; D004318:Doxycycline
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