Zhao Ze-Hua, Fan Yu-Chen, Zhao Qi, Dou Cheng-Yun, Ji Xiang-Fen, Zhao Jing, Gao Shuai, Li Xin-You, Wang Kai
Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012 China.
Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012 China ; Institute of Hepatology, Shandong University, Wenhuaxi Road 107#, Jinan, 250012 China.
Clin Epigenetics. 2015 Oct 28;7:115. doi: 10.1186/s13148-015-0149-2. eCollection 2015.
Peroxisome proliferator-activated receptor gamma (PPAR-γ) has been demonstrated to be involved in anti-inflammatory reactions, but its role in acute-on-chronic hepatitis B liver failure (ACHBLF) is unclear. Therefore, DNA methylation patterns and expression level of PPAR-γ gene were detected in peripheral blood mononuclear cells (PBMCs) from 81 patients with ACHBLF, 50 patients with chronic hepatitis B (CHB), and 30 healthy controls, and the possible role of PPAR-γ in ACHBLF was analyzed.
We found that aberrant PPAR-γ promoter methylation was attenuated in ACHBLF patients compared with CHB patients and was responsible for the elevated PPAR-γ expression level, which was negatively correlated with total bilirubin and international normalized ratio. Plasma level of TNF-α and IL-6 in ACHBLF patients were higher than CHB patients and healthy controls and significantly reduced in unmethylated group. ACHBLF patients with PPAR-γ promoter methylation had poorer outcomes than those without. Correspondingly, PPAR-γ messenger RNA (mRNA) level was higher in survivors than non-survivors and gradually increased in survivors with time, while remained low level in non-survivors.
Aberrant promoter methylation decline and PPAR-γ expression rebound occurred in ACHBLF compared with CHB and could improve prognosis of ACHBLF by negatively regulating cytokines.
过氧化物酶体增殖物激活受体γ（PPAR-γ）已被证明参与抗炎反应，但其在慢性乙型肝炎急性肝衰竭（ACHBLF）中的作用尚不清楚。因此，检测了81例ACHBLF患者、50例慢性乙型肝炎（CHB）患者和30例健康对照者外周血单个核细胞（PBMC）中PPAR-γ基因的DNA甲基化模式和表达水平，并分析了PPAR-γ在ACHBLF中的可能作用。
我们发现，与CHB患者相比，ACHBLF患者PPAR-γ启动子异常甲基化减弱，这导致了PPAR-γ表达水平升高，且该表达水平与总胆红素和国际标准化比值呈负相关。ACHBLF患者血浆TNF-α和IL-6水平高于CHB患者和健康对照者，且在未甲基化组中显著降低。PPAR-γ启动子甲基化的ACHBLF患者预后比未甲基化者差。相应地，幸存者的PPAR-γ信使核糖核酸（mRNA）水平高于非幸存者，且幸存者随时间逐渐升高，而非幸存者则维持在低水平。
与CHB相比，ACHBLF中出现启动子异常甲基化下降和PPAR-γ表达反弹，且PPAR-γ可通过负调节细胞因子改善ACHBLF的预后。
