Epidermal growth factor receptor (EGFR) is conventionally known to play a crucial role in hepatocyte proliferation, liver regeneration and is also associated with hepatocellular carcinogenesis. In addition to these proliferative roles, EGFR has also implicated in apoptotic cell death signaling in various hepatic cells, mitochondrial dysfunction and acute liver necrosis in a clinically relevant murine model of acetaminophen overdose, warranting further comprehensive exploration of this paradoxical role of EGFR in hepatotoxicity. Apart from ligand dependent activation, EGFR can also be activated in ligand-independent manner, which is mainly associated to liver injury. Recent evidence has also emerged demonstrating important role of EGFR in lipid and fatty acid metabolism in quiescent and regenerating liver. Based on these findings, EGFR has also been shown to play an important role in steatosis in clinically relevant murine NAFLD models via regulating master transcription factors governing fatty acid synthesis and lipolysis. Moreover, several lines of evidences indicate that EGFR is also involved in hepatocellular injury, oxidative stress, inflammation, direct stellate cell activation and fibrosis in chronic liver injury models, including repeated CCl4 exposure, high-fat diet and fast-food diet models. In addition to briefly summarizing role of EGFR in liver regeneration, this review comprehensively discusses all these non-conventional emerging roles of EGFR. Considering evidences of multi-facet role of EGFR at various levels in these pathophysiological process, EGFR can be a promising therapeutic target for various liver diseases, including acute liver failure and NAFLD, requiring further exploration. These roles of EGFR are relevant for alcoholic liver diseases (ALD) as well, thus providing a valid rationale for future investigations exploring a role of EGFR in ALD.

中文翻译：

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表皮生长因子受体在肝损伤和脂质代谢中的作用：旧受体的新兴作用。

众所周知，表皮生长因子受体（EGFR）在肝细胞增殖，肝脏再生中起关键作用，并且还与肝细胞癌变有关。除了这些增生作用外，在对乙酰氨基酚过量的临床相关鼠模型中，EGFR还涉及各种肝细胞的凋亡细胞死亡信号传导，线粒体功能障碍和急性肝坏死，因此有必要进一步全面探讨EGFR在肝毒性中的这种反常作用。除了依赖配体的激活外，EGFR还可以不依赖配体的方式被激活，这主要与肝损伤有关。最近的证据也表明，EGFR在静止和再生肝脏的脂质和脂肪酸代谢中具有重要作用。根据这些发现，通过调节控制脂肪酸合成和脂解作用的主转录因子，EGFR在临床相关的鼠类NAFLD模型中也可在脂肪变性中发挥重要作用。此外，一些证据表明，EGFR在慢性肝损伤模型中也参与肝细胞损伤，氧化应激，炎症，直接星状细胞活化和纤维化，包括反复暴露于CCl4，高脂饮食和快餐饮食模型。除了简要总结EGFR在肝再生中的作用外，本综述全面讨论了EGFR的所有这些非常规新兴作用。考虑到在这些病理生理过程中EGFR在各个层面均具有多方面的作用的证据，EGFR可能成为各种肝脏疾病（包括急性肝衰竭和NAFLD）的有希望的治疗靶点，需要进一步探索。EGFR的这些作用也与酒精性肝病（ALD）有关，因此为将来研究EGFR在ALD中的作用提供了有效的理论依据。