1. Podocyte and endothelial cell injury lead to nephrotic syndrome in proliferative lupus nephritis
- Author
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Toshiyuki Nakayama, Shohei Shimajiri, Satoshi Hisano, Ke-Yong Wang, Yoshiya Tanaka, and Aya Nawata
- Subjects
Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Nephrotic Syndrome ,Histology ,Adolescent ,Sialoglycoproteins ,Kidney Glomerulus ,Lupus nephritis ,Pathology and Forensic Medicine ,Podocyte ,Nephrin ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Membranous nephropathy ,medicine ,Humans ,Child ,WT1 Proteins ,Aged ,biology ,Podocytes ,Glomerular basement membrane ,Microfilament Proteins ,Endothelial Cells ,General Medicine ,Middle Aged ,medicine.disease ,Lupus Nephritis ,Proteinuria ,030104 developmental biology ,medicine.anatomical_structure ,Podocalyxin ,chemistry ,030220 oncology & carcinogenesis ,Disease Progression ,biology.protein ,Female ,Synaptopodin ,Nephrotic syndrome - Abstract
Aims Nephrotic syndrome (NS) is a major manifestation of lupus nephritis (LN). The dysregulation of podocytes, the glomerular basement membrane (GBM) and endothelial cells (ECs) results in proteinuria in glomerular diseases. The aim of our study was to clarify whether the dysregulation of these barriers is associated with NS in proliferative LN and membranous LN. Methods and results Fifty-six patients with NS, including minimal change NS in 15, primary membranous nephropathy (PMN) in 13, class III/IV LN in 15, and class V LN in 13, were enrolled in this study. Subjects with idiopathic haematuria were assigned as controls. Glomerular expression of Wilms tumour protein 1 (WT1), nephrin, synaptopodin and podocalyxin was evaluated by immunohistochemistry (IHC) and real-time quantitative reverse transcription polymerase chain reaction. EC injury was evaluated by CD31 immunostaining and electron microscopy (EM). Reduced expression of WT1, nephrin and synaptopodin was found in PMN, class III/IV LN and class V LN as compared with controls by IHC and mRNA analysis. Reduced expression of these molecules was not different between class III/IV LN and class V LN. Reduced numbers of CD31-positive ECs were found in class III/IV LN as compared with class V LN. EC injury showing subendothelial widening on EM was apparent in class III/IV LN as compared with class V LN. Foot process effacement was found only along the GBM showing EC injury in class III/IV LN. Conclusions Our study suggests that coexistence of podocyte and EC injury may lead to NS in proliferative LN. Podocyte damage alone leads to NS in membranous LN.
- Published
- 2018