Proximal tubules have the capacity to regulate uptake of albumin

Mark C. Wagner, Silvia B. Campos-Bilderback, Mahboob Chowdhury, Brittany Flores, Xianyin Lai, Jered Myslinski, Sweekar Pandit, Ruben M. Sandoval, Sarah E. Wean, Yuan Wei, Lisa M. Satlin, Roger C. Wiggins, Frank A. Witzmann, Bruce A. Molitoris

Research output: Contribution to journalArticle

38 Scopus citations

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 inATP 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.

Original languageEnglish (US)
Pages (from-to)482-494
Number of pages13
JournalJournal of the American Society of Nephrology
Volume27
Issue number2
DOIs
StatePublished - Feb 2016

    Fingerprint

ASJC Scopus subject areas

  • Nephrology

Cite this

Wagner, M. C., Campos-Bilderback, S. B., Chowdhury, M., Flores, B., Lai, X., Myslinski, J., Pandit, S., Sandoval, R. M., Wean, S. E., Wei, Y., Satlin, L. M., Wiggins, R. C., Witzmann, F. A., & Molitoris, B. A. (2016). Proximal tubules have the capacity to regulate uptake of albumin. Journal of the American Society of Nephrology, 27(2), 482-494. https://doi.org/10.1681/ASN.2014111107