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Activation of Kupffer cells (KCs) plays a pivotal role in the pathogenesis of liver fibrosis. The progression and reversal of CCl4-induced mouse liver fibrosis showed a mixed induction of hepatic classical (M1) and alternative (M2) macrophage markers. Although the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in modulating myeloid cell activation has recently been identified, its function in macrophage activation during hepatic fibrosis remains to be fully appreciated. In our study, PTEN expression of KCs was remarkably decreased in CCl4-induced mice but increased to a near-normal level in reversed mice. Moreover, PTEN was significantly decreased in IL4-induced RAW 264.7 cells in vitro and lower expression of PTEN was observed in M2 macrophages in vivo. In addition, loss- and gain-of-function studies suggested that PTEN regulates M2 macrophages polarization via activation of PI3K/Akt/STAT6 signaling, but had a limited effect on M1 macrophages polarization in vitro. Additionally, Ly294002, a chemical inhibitor of PI3K/Akt, could dramatically down-regulate the hallmarks of M2 macrophages. In conclusion, PTEN mediates macrophages activation by PI3K/Akt/STAT6 signaling pathway, which provides novel compelling evidences on the potential of PTEN in liver injury and opens new cellular target for the pharmacological therapy of liver fibrosis.

Background An increase in alcohol consumption and related harmful effects has been reported among the elderly population in Asia. Of note, it is important to monitor patterns of alcohol use, and to establish a valid and reliable evaluation system when screening for risky consumption in this age group. Objective The aim of the current study was to evaluate the possible alcoholic liver disease (ALD) risk factors of a local population in elderly Chinese adults. Methods A questionnaire was sent to 3393 Chinese adults over 40 years old in Hefei. Alcohol consumption was determined based on the AUDIT questionnaire. ALD was defined by ALD diagnostic standards. Adjusted odds ratios and 95% confidence intervals (95% CI) derived from multiple logistic regression models were used to assess the relationship between ALD and sociodemographic variables. Results Among 2545 total interviewees, 448 (17.6%) reported a history of alcohol consumption in the previous 12 months. Of these drinkers, 46.7% were male and 53.3% were female. The overall Cronbach's alpha coefficient for AUDIT was 0.648. The rate of ALD was 6.83%. Alcohol abuse was significantly associated with ALD. In the logistical model, alcohol abuse was independently associated with ALD (OR = 6.17, 95% CI: 3.69–15.24; p Conclusions Alcohol use, sex, age, and facial flushing were risk factors for ALD. These results provide important evidence for the prevention and therapy of ALD.