Abstract
BackgroundPeroxisome 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.ResultsWe 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.ConclusionsAberrant promoter methylation decline and PPAR-γ expression rebound occurred in ACHBLF compared with CHB and could improve prognosis of ACHBLF by negatively regulating cytokines.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-015-0149-2) contains supplementary material, which is available to authorized users.
Highlights
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
We found that methylation frequency of both CpG islands in CHB patients was prominently higher than healthy controls
Correlation between increased PPAR-γ messenger RNA (mRNA) level and clinical parameters in patients with ACHBLF we found that PPAR-γ mRNA level was significantly elevated in ACHBLF patients compared with CHB patients (Z = −4.003, P < 0.001) (Fig. 2a)
Summary
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. Reactivation of HBV infection is a major cause for acute deterioration of liver function manifesting as jaundice and coagulopathy, which is a severe life-threatening condition termed acute-on-chronic hepatitis B liver failure (ACHBLF) [2]. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a member of nuclear receptor supergene family that functions in ligand-dependent transcription [7, 8]. The PPAR-γ is abundantly expressed in adipose tissue, colon, spleen, and macrophages and is believed to play a role in adipocyte differentiation, lipid metabolism, and glucose homeostasis by exerting effect on gene transcription [9,10,11,12]. Accumulating evidence has demonstrated that PPAR-γ is involved in anti-
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