1. The effectiveness of chitosan-mediated silencing of PDGF-B and PDGFR-β in the mesangial proliferative glomerulonephritis therapy.
- Author
-
Alan S, Şalva E, Yılmaz İ, Turan SÖ, and Akbuğa J
- Subjects
- Animals, Apoptosis genetics, Disease Models, Animal, Glomerulonephritis genetics, Glomerulonephritis metabolism, Humans, Male, Mesangial Cells pathology, Nanoparticles chemistry, Proto-Oncogene Proteins c-sis metabolism, RNA, Small Interfering chemistry, Rats, Sprague-Dawley, Receptor, Platelet-Derived Growth Factor beta metabolism, Cell Proliferation genetics, Chitosan chemistry, Glomerulonephritis therapy, Mesangial Cells metabolism, Proto-Oncogene Proteins c-sis genetics, RNA Interference, RNA, Small Interfering genetics, Receptor, Platelet-Derived Growth Factor beta genetics
- 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-β 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-β nanoplexes in glomerulonephritic rats were studied by molecular, biochemical, and histopathologic evaluations. Chitosan/siPDGF-B + siPDGFR-β nanoplexes markedly reduced PDGF-B and PDGFR-β mRNA and protein expressions in experimental MsPGN model. Histopathologic examination results showed that the silencing of PDGF-B and its receptor PDGFR-β led to reduction in mesangial cell proliferation and matrix accumulation. The use of chitosan/siPDGF-B + siPDGFR-β nanoplexes for silencing the PDGF-B pathway in MsPGN can be considered as a new effective therapeutic strategy., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF