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Apolipoprotein C‐I plays a role in the pathogenesis of glomerulosclerosis
Author(s) -
Bus Pascal,
Pierneef Louise,
Bor Rosalie,
Wolterbeek Ron,
van Es Leendert A,
Rensen Patrick CN,
de Heer Emile,
Havekes Louis M,
Bruijn Jan A,
Berbée Jimmy F,
Baelde Hans J
Publication year - 2017
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4859
Subject(s) - diabetic nephropathy , nephropathy , glomerulosclerosis , medicine , endocrinology , pathogenesis , albuminuria , kidney , cytokine , kidney disease , diabetes mellitus , glomerulonephritis , proteinuria
Diabetic nephropathy is the leading cause of end‐stage renal disease. Diabetic patients have increased plasma concentrations of apolipoprotein C‐I ( apoCI ), and meta‐analyses found that a polymorphism in APOC1 is associated with an increased risk of developing nephropathy. To investigate whether overexpressing apoCI contributes to the development of kidney damage, we studied renal tissue and peritoneal macrophages from APOC1 transgenic ( APOC1 ‐ tg) mice and wild‐type littermates. In addition, we examined renal material from autopsied diabetic patients with and without diabetic nephropathy and from autopsied control subjects. We found that APOC1 ‐tg mice, but not wild‐type mice, develop albuminuria, renal dysfunction, and glomerulosclerosis with increased numbers of glomerular M1 macrophages. Moreover, compared to wild‐type macrophages, stimulated macrophages isolated from APOC1 ‐tg mice have increased cytokine expression, including TNF ‐alpha and TGF ‐beta, both of which are known to increase the production of extracellular matrix proteins in mesangial cells. These results suggest that APOC1 expression induces glomerulosclerosis, potentially by increasing the cytokine response in macrophages. Furthermore, we detected apoCI in the kidneys of diabetic patients, but not in control kidneys. Moreover, patients with diabetic nephropathy have significantly more apoCI present in glomeruli compared to diabetic patients without nephropathy, suggesting that apoCI could be involved in the development of diabetic nephropathy. ApoCI co‐localized with macrophages. Therefore, apoCI is a promising new therapeutic target for patients at risk of developing nephropathy. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.