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- Title
Targeted delivery of celastrol to mesangial cells is effective against mesangioproliferative glomerulonephritis.
- Authors
Ling Guo; Shi Luo; Zhengwu Du; Meiling Zhou; Peiwen Li; Yao Fu; Xun Sun; Yuan Huang; Zhirong Zhang
- 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.
- Subjects
GLOMERULONEPHRITIS; CHRONIC kidney failure; NANOPARTICLE toxicity; ORGANS (Anatomy); EXTRACELLULAR matrix; NEPHRITIS; CELLS
- Publication
Nature Communications, 2017, Vol 8, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-017-00834-8