Podocyte-specific NF-κB inhibition ameliorates proteinuria in adriamycin-induced nephropathy in mice

Maho Yamashita, Tadashi Yoshida, Sayuri Suzuki, Koichiro Honma, Matsuhiko Hayashi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Podocytes play a central role in the formation of the glomerular filtration barrier in the kidney, and their dysfunction has been shown to result in proteinuria. In the present study, we sought to determine the cell-autonomous role of NF-κB, a proinflammatory signaling, within podocytes in proteinuric kidney disease. Methods: Podocyte-specific IκBΔN transgenic (Pod-IκBΔN) mice, in which NF-κB was inhibited specifically in podocytes, were generated by the Cre-loxP technology, and their phenotype was compared with control mice in adriamycin-induced nephropathy. Results: Pod-IκBΔN mice were phenotypically normal and did not exhibit proteinuria at the physiological condition. By the intravenous administration of adriamycin, overt proteinuria appeared in Pod-IκBΔN mice, as well as in control mice. However, of interest, the amount of proteinuria was significantly lower in adriamycin-injected Pod-IκBΔN mice (373 ± 122 mg albumin/g creatinine), compared with adriamycin-injected control mice (992 ± 395 mg albumin/g creatinine). Expression of podocyte-selective slit diaphragm-associated proteins, such as nephrin and synaptopodin, was markedly decreased by adriamycin injection in control mice, whereas the reduction was attenuated in Pod-IκBΔN mice. Adriamycin-induced reduction in synaptopodin expression was also seen in cultured podocytes derived from control mice, but not in those from Pod-IκBΔN mice. Conclusions: Because nephrin and synaptopodin are essential for the maintenance of the slit diaphragm in podocytes, these results suggest that proteinuria in adriamycin-induced nephropathy is caused by the reduction in expression of these proteins. The results also suggest that the NF-κB signalling in podocytes cell-autonomously contributes to proteinuria through the regulation of these proteins.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalClinical and Experimental Nephrology
DOIs
Publication statusAccepted/In press - 2016 Apr 18

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Podocytes
Proteinuria
Doxorubicin
Transgenic Mice
Diaphragm
Albumins
Creatinine
Glomerular Filtration Barrier
Proteins
Kidney Diseases
Intravenous Administration

Keywords

  • Albuminuria
  • Kidney
  • NF-κB
  • Podocyte

ASJC Scopus subject areas

  • Nephrology
  • Physiology
  • Physiology (medical)

Cite this

Podocyte-specific NF-κB inhibition ameliorates proteinuria in adriamycin-induced nephropathy in mice. / Yamashita, Maho; Yoshida, Tadashi; Suzuki, Sayuri; Honma, Koichiro; Hayashi, Matsuhiko.

In: Clinical and Experimental Nephrology, 18.04.2016, p. 1-11.

Research output: Contribution to journalArticle

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