Dendrin location in podocytes is associated with disease progression in animal and human glomerulopathy

Katsuhiko Asanuma, Miyuki Akiba-Takagi, Fumiko Kodama, Rin Asao, Yoshiko Nagai, Aida Lydia, Hiromitsu Fukuda, Eriko Tanaka, Terumi Shibata, Hisatsugu Takahara, Teruo Hidaka, Etsuko Asanuma, Eiki Kominami, Takashi Ueno, Yasuhiko Tomino

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)537-549
Number of pages13
JournalAmerican Journal of Nephrology
Volume33
Issue number6
DOIs
Publication statusPublished - Jun 2011

Keywords

  • Adriamycin mice
  • Apoptosis
  • Dendrin
  • Glomerulosclerosis
  • Nephrosis
  • Podocyte

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