Min Robert W M, Aung Filbert W M, Liu Bryant, Arya Aliza, Win Sanda
Rush Medical College, Rush University, Chicago, IL 60612, USA.
Brown University, Providence, RI 02912, USA.
Biomedicines. 2022 Aug 20;10(8):2035. doi: 10.3390/biomedicines10082035.
Non-alcoholic fatty liver (NAFL) is the most common chronic liver disease. Activation of mitogen-activated kinases (MAPK) cascade, which leads to c-Jun N-terminal kinase (JNK) activation occurs in the liver in response to the nutritional and metabolic stress. The aberrant activation of MAPKs, especially c-Jun-N-terminal kinases (JNKs), leads to unwanted genetic and epi-genetic modifications in addition to the metabolic stress adaptation in hepatocytes. A mechanism of sustained P-JNK activation was identified in acute and chronic liver diseases, suggesting an important role of aberrant JNK activation in NASH. Therefore, modulation of JNK activation, rather than targeting JNK protein levels, is a plausible therapeutic application for the treatment of chronic liver disease.
非酒精性脂肪肝（NAFL）是最常见的慢性肝病。丝裂原活化蛋白激酶（MAPK）级联反应的激活会导致c-Jun氨基末端激酶（JNK）的激活，这种激活在肝脏中是对营养和代谢应激的反应。MAPKs的异常激活，尤其是c-Jun氨基末端激酶（JNKs），除了导致肝细胞代谢应激适应外，还会导致不必要的基因和表观遗传修饰。在急性和慢性肝病中发现了持续的P-JNK激活机制，这表明异常的JNK激活在非酒精性脂肪性肝炎（NASH）中起重要作用。因此，调节JNK激活，而不是针对JNK蛋白水平，是治疗慢性肝病的一种可行的治疗方法。
