Roles and mechanisms of NRG1 in modulating the pathogenesis of NAFLD through ErbB3 signaling in hepatocytes (NRG1 modulates NAFLD through ErbB3 signaling)

Background: Nonalcoholic fatty liver disease (NAFLD) is an emerging chronic liver disease. However, the underlying mechanisms remained poorly understood. Neuregulin (NRG) family participate in energy metabolism, and might be related to NAFLD.

Methods: L02 cells were exposed to oleic acid to establish a cellular model of NAFLD. We analyzed the NAFLD cells with NRG1 and subsequent ErbB3 siRNA treatment. Cellular total lipid was stained by Oil Red O, while triglyceride content and inflammation markers were measured by enzymatic kits. The expressions of down-stream molecules were evaluated by western blot.

Results: In vitro, NRG1 could alleviate the steatosis of NAFLD, and inhibit the expression of IL-6 and TNF-α. The downregulation of ErbB3 aggravated steatosis, improved the levels of triglyceride, IL-6 and TNF-α in NRG1-treated NAFLD. Moreover, NRG1 treatment up-regulated ErbB3 phosphorylation, and increased the expression of PI3K and phosphorylation-AKT. When NRG1-treated NAFLD cells were transfected with ErbB3 siRNA, the expressions of ErbB3, p-ErbB3, p-AKT and PI3K were all reduced.

Conclusion: NRG1 might play a protective role in the pathogenesis of NAFLD through ErbB3 phosphorylation to modulate the activation of PI3K-AKT pathway. The findings will expand the understanding of the mechanisms of NAFLD, and provide potential therapeutic targets.