Your browser doesn't support javascript.
loading
Reduction of Dimethylnitrosamine-Induced Liver Fibrosis by the Novel Gene Regulator PI Polyamide Targeting Transforming Growth Factor ß1 Gene.
Inami, Makiko; Fukushima, Akiko; Ueno, Takahiro; Yamada, Tsutomu; Tsunemi, Akiko; Matsumoto, Yoshiaki; Fukuda, Noboru; Soma, Masayoshi; Moriyama, Mitsuhiko.
Afiliação
  • Inami M; Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine.
Biol Pharm Bull ; 38(12): 1836-42, 2015.
Article em En | MEDLINE | ID: mdl-26377734
Pyrrole-imidazole (PI) polyamide is a novel gene regulating agent that competitively inhibits transcription factor binding to the promoter of the specific target gene. Liver fibrosis is an integral stage in the development of chronic liver disease, and transforming growth factor ß (TGFß) is known to play a central role in the progression of this entity. The aim of this study was to evaluate the effect of PI polyamide targeting TGFß1 on rat liver fibrosis. PI polyamide was designed to inhibit activator protein 1 (AP-1) transcription factor binding to the TGFß1 gene promoter. The effect of PI polyamide on hepatic stellate cells was evaluated by real time polymerase chain reaction (PCR) in RI-T cells. To determine the effect of PI polyamide in vivo, PI polyamide was intravenously administered at a dose of 3 mg/kg/week in dimethylnitrosamine (DMN)-induced rat model of liver fibrosis. Treatment of RI-T cells with 1.0 µM PI polyamide targeting TGFß1 significantly inhibited TGFß1 mRNA expression. Azan staining showed that DMN treatment significantly increased areas of fibrous materials compared with controls. PI polyamide targeting TGFß1 significantly decreased the fibrous area compared with DMN group. mRNA expression levels of α-smooth muscle actin and matrix metalloproteinase-2 were significantly increased in DMN-treated group compared with control. Treatment with TGFß1 PI polyamide significantly decreased mRNA expression of these genes compared with DMN group. The novel gene regulator PI polyamide targeting TGFß1 may be a feasible therapeutic agent for the treatment of chronic liver disease.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirróis / Fator de Crescimento Transformador beta / Inativação Gênica / Doença Hepática Terminal / Imidazóis / Fígado / Cirrose Hepática Experimental Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirróis / Fator de Crescimento Transformador beta / Inativação Gênica / Doença Hepática Terminal / Imidazóis / Fígado / Cirrose Hepática Experimental Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2015 Tipo de documento: Article