NAGASHIMA Youji    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Professor (Fixed Term)
Article types	Original article
Language	English
Peer review	Non peer reviewed
Title	Overexpression of Plasmalemmal Vesicle-Associated Protein-1 Reflects Glomerular Endothelial Injury in Cases of Proliferative Glomerulonephritis with Monoclonal IgG Deposits.
Journal	Formal name：Kidney international reports. Abbreviation：Kidney Int Rep ISSN code：24680249
Volume, Issue, Page	8(1),pp.151-163
Author and coauthor	Sawada Anri, Kawanishi Kunio, Igarashi Yuto, Taneda Sekiko, Hattori Motoshi, Ishida Hideki, Tanabe Kazunari, Koike Junki, Honda Kazuho, Nagashima Yoji, Nitta Kosaku
Publication date	2022/10/19
Summary	INTRODUCTION:Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) occasionally presents refractory nephrotic syndrome resulting in poor renal prognosis, but its etiology is not fully elucidated. Given that glomerular endothelial cell (GEC) stress or damage may lead to podocytopathy and subsequent proteinuria, as in thrombotic microangiopathy (TMA), diabetic kidney disease, and focal segmental glomerulosclerosis, we investigated the evidence of glomerular endothelial injury by evaluating the expression of plasmalemmal vesicle-associated protein-1 (PV-1), a component of caveolae in the cases of PGNMID.METHODS:We measured the immunofluorescent PV-1 intensities of 23 PGNMID cases and compared with those of primary membranoproliferative glomerulonephritis (MPGN) (n = 5) and IgA nephropathy (IgAN) (n = 54) cases. PV-1 localization was evaluated with Caveolin-1, and CD31 staining, and the ultrastructural analysis was performed using a low-vacuum scanning electron microscope (LVSEM). To check the association of podocyte injury, we also conducted 8-oxoguanine and Wilms tumor 1 (WT1) double stain. We then evaluated PV-1 expression in other glomerulitis and glomerulopathy such as lupus nephritis and minimal change disease.RESULTS:The intensity of glomerular PV-1 expression in PGNMID is significantly higher than that in the other glomerular diseases, although the intensity is not associated with clinical outcomes such as urinary protein levels or renal prognosis. Immunostaining and LVSEM analysis revealed that glomerular PV-1 expression is localized in GECs in PGNMID. 8-oxoguanine accumulation was detected in WT1-positive podocytes but not in PV-1-expressing GECs, suggesting GEC-derived podocyte injury in PGNMID.CONCLUSION:PV-1 overexpression reflects glomerular endothelial injury, which could be associated with podocyte oxidative stress in PGNMID cases.
DOI	10.1016/j.ekir.2022.10.010
PMID	36644361