A disintegrin and metalloprotease (ADAM) 17 is a membrane bound protease, involved in the cleavage and thus regulation of various membrane proteins, which are critical during liver injury. Among ADAM17 substrates are tumor necrosis factor α (TNFα), tumor necrosis factor receptor 1 and 2 (TNFR1, TNFR2), the epidermal growth factor receptor (EGFR) ligands amphiregulin (AR) and heparin-binding-EGF-like growth factor (HB-EGF), the interleukin-6 receptor (IL-6R) and the receptor for a hepatocyte growth factor (HGF), c-Met. TNFα and its binding receptors can promote liver injury by inducing apoptosis and necroptosis in liver cells. Consistently, hepatocyte specific deletion of ADAM17 resulted in increased liver cell damage following CD95 stimulation. IL-6 trans-signaling is critical for liver regeneration and can alleviate liver damage. EGFR ligands can prevent liver damage and deletion of amphiregulin and HB-EGF can result in increased hepatocyte death and reduced proliferation. All of which indicates that ADAM17 has a central role in liver injury and recovery from it. Furthermore, inactive rhomboid proteins (iRhom) are involved in the trafficking and maturation of ADAM17 and have been linked to liver damage. Taken together, ADAM17 can contribute in a complex way to liver damage and injury.

中文翻译：

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ADAM17在肝损伤中的作用

去整合素和金属蛋白酶 (ADAM) 17 是一种膜结合蛋白酶，参与切割和调节各种膜蛋白，这在肝损伤过程中至关重要。ADAM17 底物包括肿瘤坏死因子 α (TNFα)、肿瘤坏死因子受体 1 和 2 (TNFR1、TNFR2)、表皮生长因子受体 (EGFR) 配体双调蛋白 (AR) 和肝素结合 EGF 样生长因子 (HB -EGF)、白细胞介素 6 受体 (IL-6R) 和肝细胞生长因子 (HGF) 受体 c-Met。TNFα及其结合受体可通过诱导肝细胞凋亡和坏死性凋亡来促进肝损伤。一致地，ADAM17 的肝细胞特异性缺失导致 CD95 刺激后肝细胞损伤增加。IL-6 转信号对肝再生至关重要，可以减轻肝损伤。EGFR 配体可以防止肝损伤和双调蛋白的缺失，而 HB-EGF 可以导致肝细胞死亡增加和增殖减少。所有这些都表明 ADAM17 在肝损伤和从中恢复中具有核心作用。此外，非活性菱形蛋白 (iRhom) 参与 ADAM17 的运输和成熟，并与肝损伤有关。总之，ADAM17 可以以复杂的方式导致肝损伤和损伤。