Upregulated expression of cardiac ankyrin-repeated protein in renal podocytes is associated with proteinuria severity in lupus nephritis

Hum Pathol. 2007 Mar;38(3):410-9. doi: 10.1016/j.humpath.2006.09.006. Epub 2007 Jan 19.

Abstract

Cardiac ankyrin-repeated protein (CARP) was originally identified as a protein specifically expressed in cardiomyocytes, but has recently been found to be upregulated in some muscle diseases including muscular dystrophy and myopathy, suggesting that CARP may be induced in some pathologic conditions. In this study, we immunohistochemically analyzed 69 renal biopsy samples from patients with glomerular diseases and 2 individuals with normal kidney. We found that CARP was expressed in renal podocytes at a high level in 10 of 13 cases of crescentic glomerulonephritis, 7 of 19 cases of diabetic nephropathy, and 12 of 20 cases of lupus nephritis, although it was not expressed in endocapillary glomerulonephritis, minimal change disease, thin basement membrane disease, membranous glomerulonephritis, and normal kidney. Interestingly, in lupus nephritis, CARP expression tended to be induced in cases exhibiting nephrotic syndrome, but less so in cases without nephrotic syndrome, suggesting that CARP expression is correlated with the severity of proteinuria. Furthermore, we found that CARP was not expressed in membranous glomerulonephritis but evidently expressed in most cases of membranous lupus nephritis. Although membranous glomerulonephritis and membranous lupus nephritis are sometimes morphologically indistinguishable, it is suggested that their pathologic mechanisms differ. Therefore, we propose that examination of CARP expression is useful for precise differential diagnosis of membranous glomerulonephritis and membranous lupus nephritis.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Child
  • Doxorubicin / toxicity
  • Female
  • Glomerulonephritis / physiopathology
  • Humans
  • Immunohistochemistry
  • Kidney / metabolism
  • Lipopolysaccharides / toxicity
  • Lupus Nephritis / physiopathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Muscle Proteins / biosynthesis*
  • Nuclear Proteins / biosynthesis*
  • Podocytes / drug effects
  • Podocytes / metabolism*
  • Proteinuria / physiopathology*
  • Repressor Proteins / biosynthesis*
  • Up-Regulation
  • Vimentin / analysis

Substances

  • ANKRD1 protein, human
  • Lipopolysaccharides
  • Muscle Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • Vimentin
  • Doxorubicin