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.
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 humanglomerulopathy. 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 humanglomerulopathy. The mean occurrence of dendrin-positive nucleus per glomerulus increased in several cases of humanglomerulopathy. CONCLUSIONS: These findings suggest that the relocation of dendrin to the podocyte nuclei is useful as a novel marker of podocyte injury in humanglomerulopathy.
Authors: Suma Yaddanapudi; Mehmet M Altintas; Andreas D Kistler; Isabel Fernandez; Clemens C Möller; Changli Wei; Vasil Peev; Jan B Flesche; Anna-Lena Forst; Jing Li; Jaakko Patrakka; Zhijie Xiao; Florian Grahammer; Mario Schiffer; Tobias Lohmüller; Thomas Reinheckel; Changkyu Gu; Tobias B Huber; Wenjun Ju; Markus Bitzer; Maria P Rastaldi; Phillip Ruiz; Karl Tryggvason; Andrey S Shaw; Christian Faul; Sanja Sever; Jochen Reiser Journal: J Clin Invest Date: 2011-09-12 Impact factor: 14.808
Authors: Astrid Weins; Jenny S Wong; John M Basgen; Ritu Gupta; Ilse Daehn; Lisette Casagrande; David Lessman; Monica Schwartzman; Kristin Meliambro; Jaakko Patrakka; Andrey Shaw; Karl Tryggvason; John Cijiang He; Susanne B Nicholas; Peter Mundel; Kirk N Campbell Journal: Am J Pathol Date: 2015-06-12 Impact factor: 4.307
Authors: Monica Schwartzman; Antoine Reginensi; Jenny S Wong; John M Basgen; Kristin Meliambro; Susanne B Nicholas; Vivette D'Agati; Helen McNeill; Kirk N Campbell Journal: J Am Soc Nephrol Date: 2015-05-26 Impact factor: 10.121