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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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
Volume42
Issue number4
DOIs
Publication statusPublished - May 2010

Fingerprint

Mesangial Cells
Sirolimus
Platelet-Derived Growth Factor
Glomerular Filtration Barrier
polycarbonate
Proteinuria
In Situ Nick-End Labeling
Cellular Structures
Therapeutics
Dimethyl Sulfoxide
Crowns
Extracellular Matrix
Smooth Muscle
Actins
Flow Cytometry

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Effects of Sirolimus on Human Mesangial Cells. / 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.

In: Transplantation Proceedings, Vol. 42, No. 4, 05.2010, p. 1344-1346.

Research output: Contribution to journalArticle

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, vol. 42, no. 4, pp. 1344-1346. https://doi.org/10.1016/j.transproceed.2010.03.122
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. / Effects of Sirolimus on Human Mesangial Cells. In: Transplantation Proceedings. 2010 ; Vol. 42, No. 4. pp. 1344-1346.
@article{150bde289b2d4999b4f6a6c13cc6c384,
title = "Effects of Sirolimus on Human Mesangial Cells",
abstract = "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",
author = "C. Esposito and R. Valentino and L. Villa and N. Serpieri and F. Mangione and F. Grosjean and V. Esposito and F. Castoldi and G. Sileno and F. Montagna and N. Maggi and M. Torreggiani and G. Marchi and {Dal Canton}, A.",
year = "2010",
month = "5",
doi = "10.1016/j.transproceed.2010.03.122",
language = "English",
volume = "42",
pages = "1344--1346",
journal = "Transplantation Proceedings",
issn = "0041-1345",
publisher = "Elsevier USA",
number = "4",

}

TY - JOUR

T1 - Effects of Sirolimus on Human Mesangial Cells

AU - Esposito, C.

AU - Valentino, R.

AU - Villa, L.

AU - Serpieri, N.

AU - Mangione, F.

AU - Grosjean, F.

AU - Esposito, V.

AU - Castoldi, F.

AU - Sileno, G.

AU - Montagna, F.

AU - Maggi, N.

AU - Torreggiani, M.

AU - Marchi, G.

AU - Dal Canton, A.

PY - 2010/5

Y1 - 2010/5

N2 - 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

AB - 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

UR - http://www.scopus.com/inward/record.url?scp=77952574850&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77952574850&partnerID=8YFLogxK

U2 - 10.1016/j.transproceed.2010.03.122

DO - 10.1016/j.transproceed.2010.03.122

M3 - Article

C2 - 20534297

AN - SCOPUS:77952574850

VL - 42

SP - 1344

EP - 1346

JO - Transplantation Proceedings

JF - Transplantation Proceedings

SN - 0041-1345

IS - 4

ER -