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Targeted delivery of celastrol to mesangial cells is effective against mesangioproliferative glomerulonephritis

Author

Listed:
  • Ling Guo

    (Sichuan University)

  • Shi Luo

    (Sichuan University)

  • Zhengwu Du

    (Sichuan University)

  • Meiling Zhou

    (Sichuan University)

  • Peiwen Li

    (Sichuan University)

  • Yao Fu

    (Sichuan University)

  • Xun Sun

    (Sichuan University)

  • Yuan Huang

    (Sichuan University)

  • Zhirong Zhang

    (Sichuan University)

Abstract

Mesangial cells-mediated glomerulonephritis is a frequent cause of end-stage renal disease. Here, we show that celastrol is effective in treating both reversible and irreversible mesangioproliferative glomerulonephritis in rat models, but find that its off-target distributions cause severe systemic toxicity. We thus target celastrol to mesangial cells using albumin nanoparticles. Celastrol-albumin nanoparticles crosses fenestrated endothelium and accumulates in mesangial cells, alleviating proteinuria, inflammation, glomerular hypercellularity, and excessive extracellular matrix deposition in rat anti-Thy1.1 nephritis models. Celastrol-albumin nanoparticles presents lower drug accumulation than free celastrol in off-target organs and tissues, thereby minimizing celastrol-related systemic toxicity. Celastrol-albumin nanoparticles thus represents a promising treatment option for mesangioproliferative glomerulonephritis and similar glomerular diseases.

Suggested Citation

  • Ling Guo & Shi Luo & Zhengwu Du & Meiling Zhou & Peiwen Li & Yao Fu & Xun Sun & Yuan Huang & Zhirong Zhang, 2017. "Targeted delivery of celastrol to mesangial cells is effective against mesangioproliferative glomerulonephritis," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00834-8
    DOI: 10.1038/s41467-017-00834-8
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