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• W2023987543 startingPage "965" @default.
• W2023987543 abstract "The short synthetic interfering RNA duplexes (siRNAs) can selectively suppress gene expression in somatic mammalian cells without nonselective toxic effects of double-stranded RNA (dsRNA). However, a selective in vivo delivery of siRNA transfer has not been reported in kidney. Here, we investigated whether injection of synthetic siRNAs via renal artery followed by electroporation could be effective and therapeutic in silencing specific gene in glomerulus. We investigated the effect of siRNA in rat cultured mesangial cells (MCs) and showed that siRNA sequence-specific suppression of transgene expression was over a 1000-fold more potent than that by antisense oligodeoxynucleotide (ASODN). Transfection of siRNA targeting luciferase into rat kidneys significantly inhibited expression of a cotransfected luciferase expression vector in vivo. The delivery of siRNA targeting enhanced green fluorescent protein (EGFP) in the transgenic 'green' rat reduced endogenous EGFP expression, mainly in glomerular MCs. Furthermore, RNAi targeting against TGF-beta1 significantly suppressed TGF-beta1 mRNA and protein expression, thereby ameliorated the progression of matrix expansion in experimental glomerulonephritis. In addition, vector-based RNAi also inhibited TGF-beta1 expression in vitro and in vivo. In conclusion, siRNA-directed TGF-beta1 silencing may be of therapeutic value in the prevention and treatment of fibrotic diseases." @default.
• W2023987543 created "2016-06-24" @default.
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• W2023987543 date "2005-02-24" @default.
• W2023987543 modified "2023-10-17" @default.
• W2023987543 title "Exploring RNA interference as a therapeutic strategy for renal disease" @default.
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• W2023987543 doi "https://doi.org/10.1038/sj.gt.3302480" @default.
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