Triplex forming oligonucleotides against type α1(I) collagen attenuates liver fibrosis induced by bile duct ligation.
Liver fibrosis is a consequence of chronic liver disorders which lead to the accumulation of extracellular matrix (ECM). Particularly, there is an increased accumulation of collagen in the fibrotic liver. We have therefore used a triplex forming oligonucleotide (TFO) against the type α1(I) collagen and evaluated, whether it can attenuate liver fibrosis induced by common bile duct ligation (CBDL) in rats. There was a significant decrease in hydroxyproline levels and Masson's trichrome staining for collagen in TFO-treated CBDL groups compared to non-treated CBDL group. There was over expression of type α1(I) collagen, α-smooth muscle actin (α-SMA) and TGF-β1 expression in the CBDL group compared to TFO-treated CBDL group. Also, the serum alanine transaminase (ALT) and aspartate transaminase (AST) concentrations were less in the TFO treated group compared to non-treated CBDL group. There was also less neutrophils accumulation in TFO treated CBDL group assayed by myeloperoxidase (MPO) assay. These results suggests that TFO can be used to downregulate type 1 collagen gene expression and can alleviate liver fibrosis induced by common bile duct ligation.
Panakanti
Ravikiran
R
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38103, USA.
Pratap
Akshay
A
Yang
Ningning
N
Jackson
John S
JS
Mahato
Ram I
RI
D000818:Animals; D002461:Cell Line, Transformed; D001651:Cholestasis, Extrahepatic / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D024042:Collagen Type I / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D003135:Common Bile Duct / Q000378:metabolism* / Q000473:pathology; D004247:DNA / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008026:Ligation; D008103:Liver Cirrhosis / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D024042:Collagen Type I; D009841:Oligonucleotides; C051802:triplex DNA; D004247:DNA
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