TGF-β1 gene silencing for treating liver fibrosis

Kun Cheng, Ningning Yang, Ram I. Mahato

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Small interfering RNA (siRNA) and short hairpin RNA (shRNA) targeting different regions of transforming growth factor β1 (TGF-β1) mRNA were designed and the silencing effect was determined after transfection into immortalized rat liver stellate cells (HSC-T6). There was not only significant decrease in TGF-β1, tissue inhibitor of metalloproteinase 1 (TIMP-1), R-smooth muscle actin (R-SMA) and type I collagen after transfection with TGF-β1 siRNAs, but also synergism in gene silencing when siRNAs targeting two different start sites were used as a pool for transfection. The two siRNA sequences which efficiently inhibited TGF-β1 gene expression were converted to shRNAs via cloning into the pSilencer1.0. There was significant decrease in TGF-β1 and TIMP-1 when HSC-T6 cells were transfected with pshRNA targeting the same regions of TGF-β1 mRNA as siRNAs. Furthermore, TGF-β1 gene silencing in HSC-T6 cells significantly decreased the levels of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). In conclusion, both siRNA and shRNA showed sequence-specific and dose dependent TGF-β1 gene silencing and have the potential to treat liver fibrosis.

Original languageEnglish (US)
Pages (from-to)772-779
Number of pages8
JournalMolecular Pharmaceutics
Volume6
Issue number3
DOIs
StatePublished - Jun 1 2009

Keywords

  • Hepatic stellate cells
  • Liver fibrosis
  • Transforming growth factor β1 (TGF-β1)
  • shRNA
  • siRNA

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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