Goose fatty liver may have a unique protective mechanism as it does not show a pathological injury even in the case of severe steatosis. Although NEDD4 participates in repair and regeneration of injured liver through its target proteins, its role in nonalcoholic fatty liver disease (NAFLD) remains unknown. Using qPCR and immunoblot analyses, here we found that the mRNA and protein expressions of NEDD4 were induced in goose fatty liver, compared to normal liver. The mRNA expression of PTEN and IGF1R was also induced in goose fatty liver, however, their protein expression was or tended to be suppressed. Moreover, co-immunoprecipitation analysis indicated that there was a physical association between NEDD4 and PTEN in goose liver, which was consistent with the ubiquitination of PTEN in goose fatty liver. Furthermore, NEDD4 overexpression in goose primary hepatocytes suppressed the PTEN and IGF1R protein level without significant effect on their mRNA expression. In conclusion, the increased expression of NEDD4 leads to the degradation of PTEN and IGF1R proteins through ubiquitination in goose fatty liver, suggesting that NEDD4 may protect goose fatty liver from severe steatosis associated injury via its target proteins during the development of goose fatty liver.

中文翻译：

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在鹅脂肪肝形成过程中，E3泛素连接酶NEDD4表达的增加导致其靶蛋白PTEN/IGF1R的降解。

鹅脂肪肝可能具有独特的保护机制，即使在严重脂肪变性的情况下也不会表现出病理性损伤。尽管 NEDD4 通过其靶蛋白参与受损肝脏的修复和再生，但其在非酒精性脂肪肝 (NAFLD) 中的作用仍然未知。使用 qPCR 和免疫印迹分析，我们发现与正常肝脏相比，NEDD4 的 mRNA 和蛋白质表达在鹅脂肪肝中被诱导。PTEN和IGF1R的mRNA表达在鹅脂肪肝中也被诱导，然而，它们的蛋白质表达被抑制或趋向于被抑制。此外，免疫共沉淀分析表明鹅肝中NEDD4和PTEN之间存在物理关联，这与鹅脂肪肝中PTEN的泛素化一致。此外，NEDD4在鹅原代肝细胞中的过表达抑制了 PTEN 和 IGF1R 蛋白水平，而对其 mRNA 表达没有显着影响。总之，NEDD4 表达的增加导致 PTEN 和 IGF1R 蛋白通过鹅脂肪肝中的泛素化降解，表明 NEDD4 可能在鹅脂肪肝发展过程中通过其靶蛋白保护鹅脂肪肝免受严重的脂肪变性相关损伤。