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The effectiveness of chitosan-mediated silencing of PDGF-B and PDGFR-beta in the mesangial proliferative glomerulonephritis therapy

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


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{
  "DOI": "10.1016/j.yexmp.2019.104280", 
  "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-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.", 
  "author": [
    {
      "family": "Alan", 
      "given": " Saadet"
    }, 
    {
      "family": "Salva", 
      "given": " Emine"
    }, 
    {
      "family": "Yilmaz", 
      "given": " Ismet"
    }, 
    {
      "family": "Turan", 
      "given": " Suna Ozbas"
    }, 
    {
      "family": "Akbuga", 
      "given": " Julide"
    }
  ], 
  "container_title": "EXPERIMENTAL AND MOLECULAR PATHOLOGY", 
  "id": "68529", 
  "issued": {
    "date-parts": [
      [
        2019, 
        1, 
        1
      ]
    ]
  }, 
  "title": "The effectiveness of chitosan-mediated silencing of PDGF-B and PDGFR-beta in the mesangial proliferative glomerulonephritis therapy", 
  "type": "article-journal", 
  "volume": "110"
}
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