title: Triplex forming oligonucleotides against type α1(I) collagen attenuates liver fibrosis induced by bile duct ligation.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38103, USA.
authors.forename: Ravikiran
authors.initials: R
authors.lastname: Panakanti
authors.forename: Akshay
authors.initials: A
authors.lastname: Pratap
authors.forename: Ningning
authors.initials: N
authors.lastname: Yang
authors.forename: John S
authors.initials: JS
authors.lastname: Jackson
authors.forename: Ram I
authors.initials: RI
authors.lastname: Mahato
mesh_terms: 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
chemical_list: D024042:Collagen Type I; D009841:Oligonucleotides; C051802:triplex DNA; D004247:DNA
references.citation: J Hepatol. 1998 Oct;29(4):579-88
references.pmid: 9824267
references.citation: J Clin Invest. 2003 Nov;112(9):1383-94
references.pmid: 14597764
references.citation: J Biol Chem. 2003 Mar 28;278(13):11721-8
references.pmid: 12547835
references.citation: Am J Pathol. 2003 Apr;162(4):1229-39
references.pmid: 12651615
references.citation: Nucleic Acids Res. 1998 Nov 15;26(22):5218-22
references.pmid: 9801322
references.citation: Carcinogenesis. 2010 Aug;31(8):1344-53
references.pmid: 20513670
references.citation: J Clin Invest. 2005 Feb;115(2):209-18
references.pmid: 15690074
references.citation: Gastroenterology. 2002 May;122(5):1525-8
references.pmid: 11984538
references.citation: Hepatology. 1999 Oct;30(4):968-76
references.pmid: 10498649
references.citation: AIDS. 2006 Nov 14;20(17):2225-7
references.pmid: 17086063
references.citation: Hum Mol Genet. 2001 Oct 1;10(20):2243-51
references.pmid: 11673407
references.citation: Hepatology. 2006 Aug;44(2):420-9
references.pmid: 16871591
references.citation: Tohoku J Exp Med. 2010 Apr;220(4):319-27
references.pmid: 20410683
references.citation: Am J Pathol. 2006 May;168(5):1500-12
references.pmid: 16651617
references.citation: FASEB J. 2006 Mar;20(3):444-54
references.pmid: 16507762
references.citation: Liver Int. 2008 Apr;28(4):534-45
references.pmid: 18031476
references.citation: J Gastroenterol Hepatol. 2007 Jun;22 Suppl 1:S79-84
references.pmid: 17567474
references.citation: Anal Biochem. 1967 May;19(2):249-55
references.pmid: 6048697
references.citation: J Hepatol. 2003;38 Suppl 1:S38-53
references.pmid: 12591185
references.citation: Am J Physiol Lung Cell Mol Physiol. 2010 Aug;299(2):L222-31
references.pmid: 20495078
references.citation: Cell Signal. 2007 Apr;19(4):683-94
references.pmid: 17055226
references.citation: Crit Rev Ther Drug Carrier Syst. 2007;24(2):93-146
references.pmid: 17725523
references.citation: J Hepatol. 1997 Aug;27(2):391-8
references.pmid: 9288615
references.citation: Hepatology. 1995 Aug;22(2):573-9
references.pmid: 7635427
references.citation: Mol Pharm. 2005 May-Jun;2(3):206-17
references.pmid: 15934781
references.citation: Dig Liver Dis. 2004 Nov;36(11):744-51
references.pmid: 15571005
references.citation: Biochemistry. 2007 Oct 9;46(40):11240-52
references.pmid: 17845009
references.citation: Gastroenterology. 2004 Oct;127(4):1260-2
references.pmid: 15481004
references.citation: Nucleic Acids Res. 1997 Jun 1;25(11):2182-8
references.pmid: 9153319
references.citation: Hepatology. 2001 Nov;34(5):859-67
references.pmid: 11679955
references.citation: N Engl J Med. 2004 Apr 15;350(16):1646-54
references.pmid: 15084697
references.citation: Nucleic Acids Res. 1997 Sep 1;25(17):3459-64
references.pmid: 9254704
references.citation: Hepatology. 1999 Oct;30(4):951-8
references.pmid: 10498647
references.citation: J Hepatol. 1996 May;24(5):614-21
references.pmid: 8773918
references.citation: Biochem Biophys Res Commun. 2009 Jan 16;378(3):348-53
references.pmid: 18996089
references.citation: J Clin Invest. 1990 Jun;85(6):1833-43
references.pmid: 1693377
references.citation: Cell Growth Differ. 2002 Jun;13(6):265-73
references.pmid: 12114216