title: Proximal Tubules Have the Capacity to Regulate Uptake of Albumin.
abstract: Evidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of glomerular filtration and PT uptake, we investigated these processes in two distinct animal models. In a rat model of acute exogenous albumin overload, we quantified glomerular sieving coefficients (GSC) and PT uptake of Texas Red-labeled rat serum albumin using two-photon intravital microscopy. No change in GSC was observed, but a significant decrease in PT albumin uptake was quantified. In a second model, loss of endogenous albumin was induced in rats by podocyte-specific transgenic expression of diphtheria toxin receptor. In these albumin-deficient rats, exposure to diphtheria toxin induced an increase in albumin GSC and albumin filtration, resulting in increased exposure of the PTs to endogenous albumin. In this case, PT albumin reabsorption was markedly increased. Analysis of known albumin receptors and assessment of cortical protein expression in the albumin overload model, conducted to identify potential proteins and pathways affected by acute protein overload, revealed changes in the expression levels of calreticulin, disabled homolog 2, NRF2, angiopoietin-2, and proteins involved in ATP synthesis. Taken together, these results suggest that a regulated PT cell albumin uptake system can respond rapidly to different physiologic conditions to minimize alterations in serum albumin level.
authors.affiliation: Indiana University School of Medicine, The Roudebush Veterans Affair Medical Center, Indiana Center for Biological Microscopy, Indianapolis, Indiana;
authors.forename: Mark C
authors.initials: MC
authors.lastname: Wagner
authors.affiliation: Indiana University School of Medicine, The Roudebush Veterans Affair Medical Center, Indiana Center for Biological Microscopy, Indianapolis, Indiana;
authors.forename: Silvia B
authors.initials: SB
authors.lastname: Campos-Bilderback
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan;
authors.forename: Mahboob
authors.initials: M
authors.lastname: Chowdhury
authors.affiliation: Indiana University School of Medicine, The Roudebush Veterans Affair Medical Center, Indiana Center for Biological Microscopy, Indianapolis, Indiana;
authors.forename: Brittany
authors.initials: B
authors.lastname: Flores
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana; and.
authors.forename: Xianyin
authors.initials: X
authors.lastname: Lai
authors.affiliation: Indiana University School of Medicine, The Roudebush Veterans Affair Medical Center, Indiana Center for Biological Microscopy, Indianapolis, Indiana;
authors.forename: Jered
authors.initials: J
authors.lastname: Myslinski
authors.affiliation: Indiana University School of Medicine, The Roudebush Veterans Affair Medical Center, Indiana Center for Biological Microscopy, Indianapolis, Indiana;
authors.forename: Sweekar
authors.initials: S
authors.lastname: Pandit
authors.affiliation: Indiana University School of Medicine, The Roudebush Veterans Affair Medical Center, Indiana Center for Biological Microscopy, Indianapolis, Indiana;
authors.forename: Ruben M
authors.initials: RM
authors.lastname: Sandoval
authors.affiliation: Indiana University School of Medicine, The Roudebush Veterans Affair Medical Center, Indiana Center for Biological Microscopy, Indianapolis, Indiana;
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Wean
authors.affiliation: Department of Pediatrics, The Icahn School of Medicine at Mount Sinai, New York;
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Pediatrics, The Icahn School of Medicine at Mount Sinai, New York;
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Satlin
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan;
authors.forename: Roger C
authors.initials: RC
authors.lastname: Wiggins
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Witzmann
authors.affiliation: Indiana University School of Medicine, The Roudebush Veterans Affair Medical Center, Indiana Center for Biological Microscopy, Indianapolis, Indiana; Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana bmolitor@iu.edu.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Molitoris
mesh_terms: D000418:Albumins / Q000493:pharmacokinetics*; D000818:Animals; D005260:Female; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000418:Albumins
keywords: albuminuria; glomerular disease; glomerulus; renal proximal tubule cell; tubular epithelium