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

• Published in: Experimental and molecular pathology 2019-10, Vol.110, p.104280, Article 104280
• Main Authors: Alan, Saadet, Şalva, Emine, Yılmaz, İsmet, Turan, Suna Özbaş, Akbuğa, Jülide
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - genetics; Cell Proliferation - genetics; Chitosan; Chitosan - chemistry; Disease Models, Animal; Glomerulonephritis - genetics; Glomerulonephritis - metabolism; Glomerulonephritis - therapy; Humans; Male; Mesangial Cells - metabolism; Mesangial Cells - pathology; MsPGN; Nanoparticles - chemistry; PDGF-B; PDGFR-β; Proto-Oncogene Proteins c-sis - genetics; Proto-Oncogene Proteins c-sis - metabolism; Rats, Sprague-Dawley; Receptor, Platelet-Derived Growth Factor beta - genetics; Receptor, Platelet-Derived Growth Factor beta - metabolism; RNA Interference; RNA, Small Interfering - chemistry; RNA, Small Interfering - genetics; siRNA
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1016/j.yexmp.2019.104280

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. [Display omitted]