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Anti‐fibrotic effects of Synthetic TGF‐β1/Smad Oligodeoxynucleotide for the simultaneous regulation of mRNA and transcription factor in animal model
Author(s) -
Park KwanKyu,
Kim JungYeon,
An HyunJin,
Kim WoonHae,
Kim KyungHyun
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.924.13
Subject(s) - smad , transforming growth factor , fibrosis , fibronectin , hepatic fibrosis , cytokine , chemistry , medicine , cancer research , biology , extracellular matrix , microbiology and biotechnology
Liver fibrosis is characterized by changes in tissue architecture and extracellular matrix composition. Transforming growth factor (TGF)‐β1 is a multifunctional cytokine that induces liver fibrosis through activation of Smad signaling pathways. To develop a therapeutic approach for fibrosis in the liver, we examined inhibition of the Smad binding site and TGF‐β1 mRNA expression using the synthetic Oligodeoxynucleotide (ODN) strategy. Liver fibrosis in animal model was induced by intraperitoneal injection of CCl 4 dissolved in corn oil for 8 weeks. The delivery of ODN was performed by injection of 10μg ODN through the mouse tail vein. Synthetic TGF‐β1/Smad ODN effectively inhibits Smad binding activity and TGF‐β1 expression. Histological results showed that treatment with synthetic TGF‐β1/Smad ODN suppresses fibrotic changes. Moreover synthetic TGF‐β1/Smad ODN reduces the expression of fibrogenic protein and inflammatory cytokines. Synthetic TGF‐β1/Smad ODN demonstrates anti‐fibrotic effects that are mediated by the suppression of fibrogenic protein and inflammatory cytokines. Therefore, synthetic TGF‐β1/Smad ODN has substantial therapeutic feasibility for the treatment of liver fibrotic diseases. Support or Funding Information This study was supported by the NRF‐2014R1A1A2008955Effects of synthetic TGF‐b1/Smad ODN in CCl4 ‐induced liver fibrosis model. Histological section of murine liver stained with H&E and Masson's trichrome 8 weeks after CCl4 administration.Inhibition of fibrosis related gene expression by synthetic TGF‐b1/Smad ODN treatment in CCl4 ‐induced liver fibrosis model. Immunohistochemical staining of α‐smooth muscle actin (α‐SMA) and fibronectin 8 weeks after CCl4 administration.