Details

Autor(en) / Beteiligte

• Asada, Kiyoshi
• Aihara, Yosuke
• Takaya, Hiroaki
• Noguchi, Ryuichi
• Namisaki, Tadashi
• Moriya, Kei
• Uejima, Masakazu
• Kitade, Mitsuteru
• Mashitani, Tsuyoshi
• Takeda, Kosuke
• Kawaratani, Hideto
• Okura, Yasushi
• Kaji, Kosuke
• Douhara, Akitoshi
• Sawada, Yasuhiko
• Nishimura, Norihisa
• Seki, Kenichiro
• Mitoro, Akira
• Yamao, Junichi
• Yoshiji, Hitoshi

Titel

DNA methylation of angiotensin Ⅱ receptor gene in nonalcoholic steatohepatitis-related liver fibrosis

Ist Teil von

• World journal of hepatology, 2016-10, Vol.8 (28), p.1194-1199

Ort / Verlag

United States: Baishideng Publishing Group Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• AIM To clarify whether Agtr1 a methylation is involved in the development of nonalcoholic steatohepatitis(NASH)-related liver fibrosis in adult rats.METHODS A choline-deficient amino acid(CDAA) diet model was employed for methylation analysis of NASH-related liver fibrosis.Agtr1 a methylation levels were measured in the livers of CDAA- and control choline-sufficient amino acid(CSAA)-fed rats for 8 and 12 wk using quantitative methylation-specific PCR.Hepatic stellate cells(HSCs) were isolated by collagenase digestion of the liver,followed by centrifugation of the crude cell suspension through a density gradient.Agtr1 a methylation and its gene expression were also analyzed during the activation of HSCs.RESULTS The mean levels of Agtr1 a methylation in the livers of CDAA-fed rats(11.5% and 18.6% at 8 and 12 wk,respectively) tended to be higher(P = 0.06 and 0.09,respectively) than those in the livers of CSAA-fed rats(2.1% and 5.3% at 8 and 12 wk,respectively).Agtr1 a was not methylated at all in quiescent HSCs,but was clearly methylated in activated HSCs(13.8%,P < 0.01).Interestingly,although Agtr1 a was hypermethylated,the Agtr1 a m RNA level increased up to 2.2-fold(P < 0.05) in activated HSCs compared with that in quiescent HSCs,suggesting that Agtr1 a methylation did not silence its expression but instead had the potential to upregulate its expression.These findings indicate that Agtr1 a methylation and its upregulation of gene expression are associated with the development of NASH-related liver fibrosis.CONCLUSION This is the first study to show that DNA methylation is potential y involved in the regulation of a renin-angiotensin system-related gene expression during liver fibrosis.