Antifibrotic effect through the regulation of transcription factor using ring type‐Sp1 decoy oligodeoxynucleotide in carbon tetrachloride‐induced liver fibrosis

Abstract

Background Liver fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM). Recent advances in the knowledge about the cellular, molecular and genetic aspects of fibrosis have opened a new era of research on liver cirrhosis. A transcription factor, Sp1, originally described as a ubiquitous transcription factor, is involved in the basal expression of ECM genes and may be important in the fibrotic processes.

Anti-fibrotic Effects via Regulation of Transcription Factor Sp1 on Hepatic Stellate Cells

“…Furthermore, the anti-fibrotic effects of Sp1 decoy ODN were observed in vitro and in vivo models of fibrosis, including renal [18], lung [22] and liver [19]. Nevertheless, no reports on the role of Sp1 decoy ODN in HSCs have been investigated.…”

“…In these decoy ODNs, Sp1 decoy ODN is found to suppress the expression of VEGF, TGF-β1 and fibronectin in kidney fibroblasts and in vivo [18]. In another report, Park et al [19] have reported that Sp1 decoy inhibits the expression of TGF-β1 and its downstream target genes in vivo model of liver fibrosis, but its action in hepatic stellate cells remains to be elucidated.…”

Inhibitory Effect of Nuclear Factor-κB Decoy Oligodeoxynucleotide on Liver Fibrosis Through Regulation of the Epithelial–Mesenchymal Transition

“…Immunohistochemical staining of liver sections was performed as described previously (Park et al, 2009). Primary antibodies used were as follows: type I collagen and fibronectin (Santa Cruz Biotechnology), TGF-b 1 (R&D Systems, Minneapolis, MN), and a-smooth muscle actin (SMA; Sigma-Aldrich, St. Louis).…”

“…The supernatant was collected and analyzed by Western blot as described previously (Park et al, 2009). Primary antibodies used were against E-cadherin, vimentin, TGF-b 1 , a-SMA, fibronectin, type I collagen, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH).…”

“…In abdominal aortic aneurysms and renal ischemia-reperfusion, the decoy ODN strategy has been reported as a novel therapeutic application for treating these disorders (Cao et al, 2004;Miyake et al, 2006). In addition, we previously demonstrated that Sp1 and chimeric decoy ODN effectively suppressed the expression of fibrosis-related genes in vivo and in vitro (Park et al, 2009;Kim et al, 2013).…”