1 Ocak 2019 Dergi makalesi Açık Erişim

Alan, Saadet; Salva, Emine; Yilmaz, Ismet; Turan, Suna Ozbas; Akbuga, Julide

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    <subfield code="a">The effectiveness of chitosan-mediated silencing of PDGF-B and PDGFR-beta in the mesangial proliferative glomerulonephritis therapy</subfield>
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    <subfield code="a">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-beta 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-B + siPDGFR-beta nanoplexes in glomerulonephritic rats were studied by molecular, biochemical, and histopathologic evaluations. Chitosan/siPDGF-B + siPDGFR-beta nanoplexes markedly reduced PDGF-B and PDGFR-beta mRNA and protein expressions in experimental MsPGN model. Histopathologic examination results showed that the silencing of PDGF-B and its receptor PDGFR-beta led to reduction in mesangial cell proliferation and matrix accumulation. The use of chitosan/siPDGF-B + siPDGFR-beta nanoplexes for silencing the PDGF-B pathway in MsPGN can be considered as a new effective therapeutic strategy.</subfield>
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    <subfield code="u">Inonu Univ, Fac Pharm, Dept Pharmaceut Biotechnol, Malatya, Turkey</subfield>
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    <subfield code="u">Inonu Univ, Fac Med, Dept Med Pathol, Malatya, Turkey</subfield>
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    <subfield code="a">10.1016/j.yexmp.2019.104280</subfield>
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