TGF-β1 gene silencing for treating liver fibrosis

Kun Cheng, Ningning Yang, Ram I. Mahato

Research output: Contribution to journalArticle

83 Citations (Scopus)

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

Fingerprint

Transforming Growth Factors
Gene Silencing
Liver Cirrhosis
Small Interfering RNA
Transfection
Tissue Inhibitor of Metalloproteinase-1
Messenger RNA
Collagen Type I
Interleukin-1beta
Smooth Muscle
Actins
Organism Cloning
Tumor Necrosis Factor-alpha
Cytokines
Gene Expression
Liver

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

TGF-β1 gene silencing for treating liver fibrosis. / Cheng, Kun; Yang, Ningning; Mahato, Ram I.

In: Molecular Pharmaceutics, Vol. 6, No. 3, 01.06.2009, p. 772-779.

Research output: Contribution to journalArticle

Cheng, Kun ; Yang, Ningning ; Mahato, Ram I. / TGF-β1 gene silencing for treating liver fibrosis. In: Molecular Pharmaceutics. 2009 ; Vol. 6, No. 3. pp. 772-779.
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