The effectiveness of chitosan-mediated silencing of PDGF-B and PDGFR-ß in the mesangial proliferative glomerulonephritis therapy.
Exp Mol Pathol
; 110: 104280, 2019 10.
Article
em En
| MEDLINE
| ID: mdl-31265815
ABSTRACT
Platelet-derived growth factor-B (PDGF-B) is a growth factor that plays an important role in the progression of mesangial proliferative glomerulonephritis (MsPGN). PDGF-B may contribute to mesangioproliferative changes and is overexpressed in MsPGN. Recently, small interfering RNAs (siRNAs) have been widely used for gene silencing effects in experimental models of renal diseases. Nanoparticle-based therapeutics are preferred for reasons such as increasing therapeutic efficacy and reducing toxic effects caused by high doses. The distribution of nanoparticles to the kidney is a significant advantage in siRNA delivery. The aim of this study was to investigate the efficacy of chitosan/siRNA nanoplexes in silencing of PDGF-B and PDGFR-ß genes in kidney and to decrease mesangial cell proliferation and matrix accumulation in MsPGN model induced by anti-Thy-1.1 antibody. The therapeutic effects of chitosan/siPDGF-Bâ¯+â¯siPDGFR-ß nanoplexes in glomerulonephritic rats were studied by molecular, biochemical, and histopathologic evaluations. Chitosan/siPDGF-Bâ¯+â¯siPDGFR-ß nanoplexes markedly reduced PDGF-B and PDGFR-ß mRNA and protein expressions in experimental MsPGN model. Histopathologic examination results showed that the silencing of PDGF-B and its receptor PDGFR-ß led to reduction in mesangial cell proliferation and matrix accumulation. The use of chitosan/siPDGF-Bâ¯+â¯siPDGFR-ß nanoplexes for silencing the PDGF-B pathway in MsPGN can be considered as a new effective therapeutic strategy.
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MEDLINE
Assunto principal:
Receptor beta de Fator de Crescimento Derivado de Plaquetas
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Proteínas Proto-Oncogênicas c-sis
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RNA Interferente Pequeno
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Interferência de RNA
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Quitosana
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Proliferação de Células
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Células Mesangiais
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Glomerulonefrite
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article