Apolipoprotein C‐I plays a role in the pathogenesis of glomerulosclerosis

Abstract

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.

iTRAQ-based comparative proteomics analysis reveals specific urinary biomarkers for various kidney diseases

“…C5 activation is also observed in patients with lupus nephritis and renal cell carcinoma, which suggests that activated C5 is widespread in kidney diseases (37,38). Since apoCI, encoded by the apoc1 gene, is expressed primarily in the liver, its plasma concentration is associated with an increased risk of developing DN, and it acts as a key factor in the pathogenesis of glomerulosclerosis (39,40). Our results further confirmed that urinary C5 is a specific marker of multiple kidney diseases.…”

Apolipoprotein C1 (APOC1): A Novel Diagnostic and Prognostic Biomarker for Clear Cell Renal Cell Carcinoma

“…In recent years, APOC1 was also reported to play significant roles in some biological processes, such as cholesterol catabolism, dendritic reorganization, and membrane remodeling (6,7). APOC1 is associated with the progression of multiple diseases, including Alzheimer's disease, glomerulosclerosis, type 1 or type 2 diabetes, and diabetic nephropathy (8)(9)(10)(11). Additionally, some studies revealed that APOC1 acts as an oncogene in the progression of some malignant tumors, including breast, pancreatic, colorectal, and lung cancer (11)(12)(13)(14)(15).…”

The Vascular Endothelial Growth Factor Inhibitor Soluble FLT-1 Ameliorates Atopic Dermatitis in APOC1 Transgenic Mice

“…In this study, we investigated the anti-inflammatory effects of sFLT-1 on AD in a mouse model. APOC1 transgenic (APOC1-tg) mice develop AD because of a disruption of the skin lipid barrier (Nagelkerken et al, 2008) and a triggered immune system (Bus et al, 2017a). While manifesting many AD hallmarks, the APOC1-tg model does not fully replicate human disease.…”