論文

査読有り 国際誌
2017年1月

Rituximab protects podocytes and exerts anti-proteinuric effects in rat adriamycin-induced nephropathy independent of B-lymphocytes.

Nephrology (Carlton, Vic.)
  • Yuichi Takahashi
  • ,
  • Yohei Ikezumi
  • ,
  • Akihiko Saitoh

22
1
開始ページ
49
終了ページ
57
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/nep.12737

AIM: This study was aimed at examining the effects of treatment with rituximab, a chimeric monoclonal antibody against the protein CD20, in a B-lymphocyte independent adriamycin-induced rat model of nephrotic syndrome. Rituximab is an emerging rescue therapy used in patients with complicated nephrotic syndrome and, therefore, we sought to elucidate the apparent B-lymphocyte independent mechanism underlying its anti-proteinuric effect. METHODS: Adriamycin-induced nephropathy was established in Wistar rats by intravenously injecting 10 mg/kg of adriamycin, which were then treated with rituximab or purified human IgG weekly and euthanized on day 28. Proteinuria, glomerular expression of sphingomyelin phosphodiesterase acid-like 3b protein, and podocyte-related proteins were examined using immunofluorescence staining and a reverse transcription-polymerase chain reaction. RESULTS: Rituximab treatment of rats with adriamycin-induced nephropathy significantly reduced urinary protein excretion 14 to 28 days after induction of disease, compared with those treated with purified normal human IgG. Furthermore, rituximab treatment also prevented the reduction of glomerular nephrin and podocin expression on day 28. Double-immunofluorescence staining revealed that after in vivo administration, rituximab was bound to the glomeruli, which also expressed synaptopodin or sphingomyelin phosphodiesterase, acid-like 3b. Moreover, sphingomyelin phosphodiesterase, acid-like 3b expression was significantly decreased on day 28 of adriamycin-induced nephropathy, which was also prevented by rituximab. CONCLUSIONS: This study demonstrated that rituximab directly affected glomerular podocytes and ameliorated proteinuria in adriamycin-induced nephropathy in rats. Furthermore, protection of podocyte function by rituximab may be mediated by direct modulation of a sphingomyelin phosphodiesterase, acid-like 3b-dependent mechanism.

リンク情報
DOI
https://doi.org/10.1111/nep.12737
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26833819
ID情報
  • DOI : 10.1111/nep.12737
  • PubMed ID : 26833819

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