Peroxisome proliferator-activated receptor-α and -γ rnRNA levels are reduced in chronic hepatitis C with steatosis and genotype 3 infection
Peroxisome proliferator-activated receptor-α and -γ rnRNA levels are reduced in chronic hepatitis C with steatosis and genotype 3 infection
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DOI：
10.1111/j.1365-2036.2006.02729.x
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发表时间：
2006-01-01
影响因子：
7.6
通讯作者：
Negro, F
中科院分区：
文献类型：
--
作者：
De Gottardi, A;Pazienza, V;Negro, F
背景：慢性丙型肝炎的脂肪变性与炎症和纤维化加速有关。目的探讨过氧化物酶体增殖物激活受体、α和γ在丙型肝炎病毒相关脂肪变性发病机制中的作用。方法测定过氧化物酶体增殖物激活受体(PPAR) α。在35例基因1型和22例基因3型感染者的肝活检和表达丙型肝炎病毒1b或3a核心蛋白的Huh7细胞中进行定量聚合酶链反应。结果基因3型患者肝脏PPAR-a mRNA水平明显低于基因1型患者。脂肪变性与基因1型的ppar - α表达降低有关，而与基因3型无关。与基因1型相比，基因3型的ppar - γ表达显著降低，脂肪变性与ppar - γ水平降低有关，但仅在基因1型中。PPARs mRNA水平与肝脏活性或纤维化无显著相关性。与丙型肝炎病毒1b相比，丙型肝炎病毒3a核心蛋白的表达与甘油三酯积累的增加和ppar - γ mRNA的显著减少有关。结论脂肪变性和丙型肝炎病毒基因3型的存在均与PPARs的显著下调有关。这些受体和其他因素似乎在丙型肝炎病毒相关脂肪变性的发病机制中起作用。
Background Steatosis in chronic hepatitis C is associated with inflammation and accelerated fibrogenesis.Aim To assess the contribution of peroxisome proliferator-activated receptor, alpha and -gamma to the pathogenesis of hepatitis C virus associated steatosis is unknown. Methods We measured peroxisome proliferator- activated receptor (PPAR)-alpha. and -gamma mRNA by quantitative polymerase chain reaction in liver biopsies of 35 genotype 1 and 22 genotype 3 infected patients and in Huh7 cells expressing hepatitis C virus 1b or 3a core protein.Results PPAR-a mRNA was significantly reduced in livers of patients with genotype 3 compared with genotype 1. Steatosis was associated to a decreased expression of PPAR-alpha in genotype 1, but not in genotype 3. PPAR-gamma expression was significantly lower in genotype 3 compared with genotype 1 and steatosis was associated to decreased levels of PPAR-gamma, but only in genotype 1. There was no significant relationship between PPARs mRNA levels and liver activity or fibrosis. Expression of the hepatitis C virus 3a core protein was associated with an increase in triglyceride accumulation and with a significant reduction of PPAR-gamma mRNA compared with hepatitis C virus 1b.Conclusions The presence of steatosis and hepatitis C virus genotype 3 are both associated with a significant down-regulation of PPARs. These receptors, and also additional factors, seem to play a role in the pathogenesis of hepatitis C virus-associated steatosis.