Effects of Sirolimus on Human Mesangial Cells

C. Esposito, R. Valentino, L. Villa, N. Serpieri, F. Mangione, F. Grosjean, V. Esposito, F. Castoldi, G. Sileno, F. Montagna, N. Maggi, M. Torreggiani, G. Marchi, A. Dal Canton

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Mesangial cell (MC) proliferation and production of extracellular matrix or loss of MC are both central findings in a number of renal proteinuric diseases. However, the role of MC as components of the glomerular filtration barrier and whether MC alterations induce changes in the glomerular filtration barrier leading to proteinuria are still matters of debate. The effects of Sirolimus (SRL) in proteinuric nephropathies is controversial: some papers have indicated a reduction and others, an increase in proteinuria after sirolimus treatment. Considering the pivotal role of MC in the pathogenesis of many chronic nephropathies, we evaluated the effect of SRL on cultured human MC. We treated primary human MC cultures with SRL, or platelet-derived growth factor (PDGF) or SRL + PDGF, or dimethylsulfoxide, the SRL vehicle, as a control. PDGF was used to activate MC. After 48 hours treatment, MC showed a significant growth increase that was significantly reduced by SRL (P <.01). Apoptosis, determined by the TUNEL assay and flow cytometry, was not modified by the treatments at 24 hours. SRL treatment increased significantly the number of α-smooth muscle actin-positive cells compared with controls (P <.05). Cells treated with SRL and SRL + PDGF showed significant changes in morphology with increased mean cell surface, perimeter, and maximum diameter (P <.01) but not protein content. Furthermore, MC treated with SRL showed decreased migration through polycarbonate membranes. The changes induced by SRL may help to explain some of the in vivo effects observed in SRL-treated patients. Crown

Original languageEnglish
Pages (from-to)1344-1346
Number of pages3
JournalTransplantation Proceedings
Issue number4
Publication statusPublished - May 2010

ASJC Scopus subject areas

  • Surgery
  • Transplantation

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    Esposito, C., Valentino, R., Villa, L., Serpieri, N., Mangione, F., Grosjean, F., Esposito, V., Castoldi, F., Sileno, G., Montagna, F., Maggi, N., Torreggiani, M., Marchi, G., & Dal Canton, A. (2010). Effects of Sirolimus on Human Mesangial Cells. Transplantation Proceedings, 42(4), 1344-1346. https://doi.org/10.1016/j.transproceed.2010.03.122