PPARγ alleviated hepatocyte steatosis through reducing SOCS3 by inhibiting JAK2/STAT3 pathway
PPARγ alleviated hepatocyte steatosis through reducing SOCS3 by inhibiting JAK2/STAT3 pathway
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PPARγ 通过抑制 JAK2/STAT3 通路减少 SOCS3 减轻肝细胞脂肪变性
DOI：
10.1016/j.bbrc.2018.03.110
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发表时间：
2018-04-15
影响因子：
3.1
通讯作者：
Mao, Jingwei
中科院分区：
文献类型：
--
作者：
Bi, Jian;Sun, Kang;Mao, Jingwei
过氧化物酶体增殖物激活受体 γ (PPAR γ) 参与胰岛素抵抗 (IR) 过程，胰岛素抵抗是非酒精性脂肪肝 (NAFLD) 的重要病理生理学过程。同时，细胞因子信号传导抑制因子 3 (SOCS3) 也调节 NAFLD 中的 IR。 PPARγ和SOCS3都通过调节IR在NAFLD中发挥作用，但尚不清楚这两种蛋白是否相互作用来调节肝脂肪变性。使用 LPS 处理的 Kuppfer 细胞 (KCs) 和棕榈酸、KC 条件培养基 (KCCM)、PPARy 激动剂罗格列酮 (ROZ) 或 JAK2 抑制剂 AG490 处理的 BRL-3A 细胞分析 PPARy、SOCS3 及其相关的 JAK2/STAT3 通路，以证明 PPARy 和 SOCS3 在肝细胞脂肪变性中的作用。随着LPS浓度的增加，KCs的吞噬活性降低；但TNF-α和IL-6的释放增加。 KCCM处理后，脂肪变性BRL-3A细胞中SOCS3、JAK2和STAT3的mRNA水平以及SOCS3、p-JAK2和p-STAT3的蛋白表达显着增加，而AG490或ROZ处理抑制了这些变化。综上所述，这些结果表明，KCs 功能障碍导致的 KCCM 通过促进 SOCS3 的表达而促进肝细胞脂肪变性。但 PPARγ 激动剂 ROZ 通过抑制肝细胞中的 JAK2/STAT3 来减少 SOCS3 的表达，从而减轻脂肪变性。 (C) 2018 Elsevier Inc. 保留所有权利。
Peroxisome proliferator-activated receptor gamma (PPAR gamma) participates in the process of insulin resistance (IR), a crucial pathophysiology in non-alcoholic fatty liver disease (NAFLD). Meanwhile, suppressor of cytokine signaling3 (SOCS3) also regulates IR in NAFLD. Both PPAR gamma and SOCS3 play a role in NAFLD through regulating IR, while it is unclear whether these two proteins interact to regulate hepatic steatosis. PPARy, SOCS3 and its associated JAK2/STAT3 pathway were analyzed using Kuppfer cells (KCs) treatment with LPS and BRL-3A cells treatment with palmitic acid, KC-conditioned medium (KCCM), PPARy agonist rosiglitazone (ROZ) or JAK2 inhibitor AG490 to demonstrate the role of PPARy and SOCS3 in hepatocytes steatosis. As LPS concentration increasing, phagocytosis activity of KCs decreased; but releasing of TNF-alpha and IL-6 increased. After treatment with KCCM, mRNA level of SOCS3, JAK2 and STAT3 as well as protein expression of SOCS3, p-JAK2 and p-STAT3 in steatosis BRL-3A cells increased significantly, which were inhibited by AG490 or ROZ treatment. Taken together, these results indicated that KCCM attributed to KCs dysfunction facilitated hepatocyte steatosis through promoting expressing SOCS3; but PPARy agonist ROZ alleviated steatosis through reducing SOCS3 expression by inhibiting JAK2/STAT3 in hepatocytes. (C) 2018 Elsevier Inc. All rights reserved.