Display options
Cite
Sun J, Hultenby K, Axelsson J, et al. Proximal Tubular Expression Patterns of Megalin and Cubilin in Proteinuric Nephropathies. Kidney Int Rep. 2017;2(4):721-732doi: 10.1016/j.ekir.2017.02.012.
Sun, J., Hultenby, K., Axelsson, J., Nordström, J., He, B., Wernerson, A., & Lindström, K. (2017). Proximal Tubular Expression Patterns of Megalin and Cubilin in Proteinuric Nephropathies. Kidney international reports, 2(4), 721-732. https://doi.org/10.1016/j.ekir.2017.02.012
Sun, Jia, et al. "Proximal Tubular Expression Patterns of Megalin and Cubilin in Proteinuric Nephropathies." Kidney international reports vol. 2,4 (2017): 721-732. doi: https://doi.org/10.1016/j.ekir.2017.02.012
Sun J, Hultenby K, Axelsson J, Nordström J, He B, Wernerson A, Lindström K. Proximal Tubular Expression Patterns of Megalin and Cubilin in Proteinuric Nephropathies. Kidney Int Rep. 2017 Mar 01;2(4):721-732. doi: 10.1016/j.ekir.2017.02.012. eCollection 2017 Jul. PMID: 29142988; PMCID: PMC5678615.
Copy Download .nbib Format: NLM
Share it on

Kidney Int Rep. 2017 Mar 01;2(4):721-732. doi: 10.1016/j.ekir.2017.02.012. eCollection 2017 Jul.

Proximal Tubular Expression Patterns of Megalin and Cubilin in Proteinuric Nephropathies.

Kidney international reports

Jia Sun, Kjell Hultenby, Jonas Axelsson, Johan Nordström, Bing He, Annika Wernerson, Karin Lindström

Affiliations

  1. Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
  2. Division of Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  3. Division of Matrix Biology, Department of Medical Biochemistry and Biophysics; Karolinska Institutet, Stockholm, Sweden.
  4. Department Clinical Immunology, Karolinska University Hospital, Stockholm, Sweden.
  5. Division of Transplantation, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
  6. Department of Transplant Surgery, Karolinska University Hospital, Stockholm, Sweden.
  7. Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
  8. Department of Nephrology, Karolinska University Hospital, Stockholm, Sweden.

PMID: 29142988 PMCID: PMC5678615 DOI: 10.1016/j.ekir.2017.02.012

Abstract

INTRODUCTION: Receptor-mediated endocytosis is responsible for protein reabsorption in the proximal tubules. For albumin this process involves at least 2 interacting receptors, megalin and cubilin. Albumin is not usually present in the urine, indicating a highly efficient tubular reuptake under physiological conditions. However, early appearance of albuminuria may mean that the tubular system is overwhelmed by large quantities of albumin or that the function is impaired.

METHODS: To better understand the physiological role of megalin and cubilin in human renal disease, renal biopsies from 15 patients with a range of albuminuria and 3 healthy living donors were analyzed for proximal tubular expression of megalin and cubilin using immunohistochemistry (IHC) and semiquantitative immune-electron microscopy. Their expression in proteinuric zebrafish was also studied.

RESULTS: Megalin and cubilin were expressed in brush border and cytoplasmic vesicles. Patients with microalbuminuric IgA nephropathy and thin membrane disease had significantly higher megalin in proximal tubules, whereas those with macro- or nephrotic-range albuminuria had unchanged levels. Cubilin expression was significantly higher in all patients. In a proteinuric zebrafish nphs2 knockdown model, we found a dose-dependent increase in the expression of tubular megalin and cubilin in response to tubular protein uptake.

DISCUSSION: Megalin and cubilin show different expression patterns in different human diseases, which indicates that the 2 tubular proteins differently cooperate in cleaning up plasma proteins in kidney tubules.

Keywords: albuminuria; cubilin; megalin; proximal tubule

References

  1. J Biol Chem. 1991 Mar 5;266(7):4489-94 - PubMed
  2. Dev Biol. 2005 Sep 15;285(2):316-29 - PubMed
  3. Nephrol Dial Transplant. 2003 Jan;18(1):70-6 - PubMed
  4. Am J Physiol Renal Physiol. 2007 Jan;292(1):F430-9 - PubMed
  5. Biogerontology. 2007 Oct;8(5):505-15 - PubMed
  6. Annu Rev Physiol. 2005;67:573-94 - PubMed
  7. Gene Expr Patterns. 2010 Sep;10(6):237-43 - PubMed
  8. Int J Nephrol. 2012;2012:481520 - PubMed
  9. Nephrol Dial Transplant. 2014 Sep;29 Suppl 4:iv113-6 - PubMed
  10. J Clin Hypertens (Greenwich). 2004 Nov;6(11 Suppl 3):2-7 - PubMed
  11. N Engl J Med. 2011 Jan 6;364(1):89-91 - PubMed
  12. Nat Rev Mol Cell Biol. 2002 Apr;3(4):256-66 - PubMed
  13. Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):7014-9 - PubMed
  14. J Am Soc Nephrol. 2002 Jan;13(1):125-33 - PubMed
  15. Haematologica. 2011 Nov;96(11):1715-9 - PubMed
  16. J Exp Med. 1988 Jan 1;167(1):213-8 - PubMed
  17. Kidney Int. 2000 Oct;58(4):1523-33 - PubMed
  18. Development. 1995 Feb;121(2):347-57 - PubMed
  19. Int J Biochem Cell Biol. 2016 Oct;79:194-198 - PubMed
  20. Nephrol Dial Transplant. 2010 Aug;25(8):2458-67 - PubMed
  21. Nephrol Dial Transplant. 2004 Feb;19(2):277-81 - PubMed
  22. Transplant Rev (Orlando). 2012 Jan;26(1):14-9 - PubMed
  23. Am J Med Genet A. 2008 Jul 15;146A(14):1842-7 - PubMed
  24. J Am Soc Nephrol. 1998 Oct;9(10):1767-76 - PubMed
  25. Kidney Int. 1995 May;47(5):1242-51 - PubMed
  26. Am J Kidney Dis. 2008 Jun;51(6):893-903 - PubMed
  27. J Am Soc Nephrol. 2007 Jun;18(6):1824-34 - PubMed
  28. Nat Genet. 1999 Mar;21(3):309-13 - PubMed
  29. J Am Soc Nephrol. 2007 Apr;18(4):1199-208 - PubMed
  30. Biol Reprod. 1996 Sep;55(3):676-83 - PubMed
  31. Br J Clin Pharmacol. 2013 Oct;76(4):516-23 - PubMed
  32. Am J Pathol. 1999 Oct;155(4):1361-70 - PubMed
  33. Nephrol Dial Transplant. 2011 Nov;26(11):3446-51 - PubMed
  34. Nephron Physiol. 2011;118(1):p1-6 - PubMed
  35. Am J Physiol Cell Physiol. 2008 Aug;295(2):C529-37 - PubMed
  36. Nephrol Dial Transplant. 2013 Mar;28(3):585-91 - PubMed
  37. J Cell Sci. 2006 May 15;119(Pt 10):2127-37 - PubMed
  38. Int Rev Cytol. 1998;180:237-84 - PubMed
  39. BMC Med Genet. 2013 Oct 24;14:111 - PubMed
  40. J Am Soc Nephrol. 2010 Nov;21(11):1859-67 - PubMed
  41. Kidney Int. 2016 Jan;89(1):58-67 - PubMed
  42. Am J Med Genet. 1993 Oct 1;47(5):679-82 - PubMed
  43. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5557-61 - PubMed
  44. Pediatr Nephrol. 2015 Jun;30(6):1027-31 - PubMed
  45. Med Mol Morphol. 2008 Jun;41(2):92-8 - PubMed
  46. Nat Genet. 2007 Aug;39(8):957-9 - PubMed
  47. Kidney Int. 2013 Apr;83(4):662-73 - PubMed
  48. Kidney Int. 1998 Jun;53(6):1608-15 - PubMed

Publication Types