Dendrin Location in Podocytes Is Associated with Disease Progression in Animal and Human GlomerulopathyAsanuma K.a · Akiba-Takagi M.a · Kodama F.a · Asao R.a · Nagai Y.a · Lydia A.a, d · Fukuda H.a · Tanaka E.a, c · Shibata T.a · Takahara H.a · Hidaka T.a · Asanuma E.a · Kominami E.b · Ueno T.b · Tomino Y.a
aDivision of Nephrology, Department of Internal Medicine, and bDepartment of Biochemistry, Juntendo University Faculty of Medicine, cDepartment of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan; dDivision of Nephrology and Hypertension, Department of Internal Medicine, Cipto Mangunkusumo Hospital, University of Indonesia, Jakarta, Indonesia Am J Nephrol 2011;33:537–549 (DOI:10.1159/000327995)
Background: Adriamycin (ADR) nephrosis in mice has been extensively studied and has enabled a greater understanding of the processes underlying the progression of renal injury. Dendrin is a novel component of the slit diaphragm with proapoptotic signaling properties, and it accumulates in the podocyte nucleus in response to glomerular injury in mice. The present study re-evaluated chronic progressive nephropathy in ADR mice and the localization of dendrin in mice and in human glomerulopathy. Methods: To investigate the localization of dendrin, a mouse model of nephrosis and glomerulosclerosis was used, in which ADR was injected once. WT-1-positive cells and apoptotic cells were counted in vivo and in vitro. To check the expression of dendrin in ADR mice, immunostaining and Western blot were performed. A survey of dendrin staining was performed on human kidney biopsy specimens. Results: The injection of ADR induced proteinuria, podocyte loss and glomerulosclerosis. It also caused the relocation of dendrin from the slit diaphragm to the podocyte nucleus. We demonstrated the location of dendrin to podocyte nuclei in several cases of human glomerulopathy. The mean occurrence of dendrin-positive nucleus per glomerulus increased in several cases of human glomerulopathy. Conclusions: These findings suggest that the relocation of dendrin to the podocyte nuclei is useful as a novel marker of podocyte injury in human glomerulopathy.
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