Role of epidermal growth factor receptor in liver injury and lipid metabolism: Emerging new roles for an old receptor

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.