Cubilin maintains blood levels of HDL and albumin

Obaidullah Aseem, Brian T. Smith, Marion A. Cooley, Brent A. Wilkerson, Kelley M. Argraves, Alan T. Remaley, W. Scott Argraves

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Cubilin is an endocytic receptor highly expressed in renal proximal tubules, where it mediates uptake of albumin and filtered forms of apoA-I/HDL. Cubilin deficiency leads to urinary loss of albumin and apoA-I; however, the consequences of cubilin loss on the homeostasis of blood albumin and apoA-I/HDL have not been studied. Using mice heterozygous for cubilin gene deletion (cubilin HT mice), we show that cubilin haploinsufficiency leads to reduced renal proximal tubular uptake of albumin and apoA-I and significantly increased urinary loss of albumin and apoA-I.Moreover, cubilin HT mice displayed significantly decreased blood levels of albumin, apoA-I, and HDL. The levels of albumin and apoA-I protein or mRNA expressed in the liver, kidney, or intestine of cubilin HT mice did not change significantly. The clearance rate of small HDL3 particles (density>1.13 g/ml) from the blood increased significantly in cubilin HT mice. In contrast, the rate of clearance of larger HDL2 particles from the blood did not change significantly, indicating a decreased half-life for HDL particles capable of filtering through the glomerulus. On the basis of these findings, we conclude that cubilin deficiency reduces renal salvage and delivery back to the blood of albumin and apoA-I, which decreases blood levels of albumin and apoA-I/HDL. These findings raise the possibility that therapeutic increase of renal cubilin expression might reduce proteinuria and increase blood levels of albumin and HDL.

Original languageEnglish (US)
Pages (from-to)1028-1036
Number of pages9
JournalJournal of the American Society of Nephrology
Volume25
Issue number5
DOIs
StatePublished - May 1 2014

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Apolipoprotein A-I
Albumins
Kidney
intrinsic factor-cobalamin receptor
Haploinsufficiency
Proximal Kidney Tubule
Gene Deletion
Proteinuria
Intestines
Half-Life
Homeostasis
Messenger RNA
Liver

ASJC Scopus subject areas

  • Nephrology

Cite this

Aseem, O., Smith, B. T., Cooley, M. A., Wilkerson, B. A., Argraves, K. M., Remaley, A. T., & Argraves, W. S. (2014). Cubilin maintains blood levels of HDL and albumin. Journal of the American Society of Nephrology, 25(5), 1028-1036. https://doi.org/10.1681/ASN.2013060671

Cubilin maintains blood levels of HDL and albumin. / Aseem, Obaidullah; Smith, Brian T.; Cooley, Marion A.; Wilkerson, Brent A.; Argraves, Kelley M.; Remaley, Alan T.; Argraves, W. Scott.

In: Journal of the American Society of Nephrology, Vol. 25, No. 5, 01.05.2014, p. 1028-1036.

Research output: Contribution to journalArticle

Aseem, O, Smith, BT, Cooley, MA, Wilkerson, BA, Argraves, KM, Remaley, AT & Argraves, WS 2014, 'Cubilin maintains blood levels of HDL and albumin', Journal of the American Society of Nephrology, vol. 25, no. 5, pp. 1028-1036. https://doi.org/10.1681/ASN.2013060671
Aseem O, Smith BT, Cooley MA, Wilkerson BA, Argraves KM, Remaley AT et al. Cubilin maintains blood levels of HDL and albumin. Journal of the American Society of Nephrology. 2014 May 1;25(5):1028-1036. https://doi.org/10.1681/ASN.2013060671
Aseem, Obaidullah ; Smith, Brian T. ; Cooley, Marion A. ; Wilkerson, Brent A. ; Argraves, Kelley M. ; Remaley, Alan T. ; Argraves, W. Scott. / Cubilin maintains blood levels of HDL and albumin. In: Journal of the American Society of Nephrology. 2014 ; Vol. 25, No. 5. pp. 1028-1036.
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