Department of Pharmacy, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea.
Int J Mol Sci. 2022 Jul 29;23(15):8387. doi: 10.3390/ijms23158387.
Nonalcoholic fatty liver disease (NAFLD) is found in up to 30% of the world's population and can lead to hepatocellular carcinoma (HCC), which has a poor 5-year relative survival rate of less than 40%. Clinical therapeutic strategies are not very successful. The co-occurrence of metabolic disorders and inflammatory environments during the development of steatohepatitis thus needs to be more specifically diagnosed and treated to prevent fatal HCC development. To improve diagnostic and therapeutic strategies, the identification of molecules and/or pathways responsible for the initiation and progression of chronic liver disease has been explored in many studies, but further study is still required. Transmembrane 4 L six family member 5 (TM4SF5) has been observed to play roles in the regulation of metabolic functions and activities in hepatocytes using in vitro cell and in vivo animal models without or with TM4SF5 expression in addition to clinical liver tissue samples. TM4SF5 is present on the membranes of different organelles or vesicles and cooperates with transporters for fatty acids, amino acids, and monocarbohydrates, thus regulating nutrient uptake into hepatocytes and metabolism and leading to phenotypes of chronic liver diseases. In addition, TM4SF5 can remodel the immune environment by interacting with immune cells during TM4SF5-mediated chronic liver diseases. Because TM4SF5 may act as an NAFLD biomarker, this review summarizes crosstalk between TM4SF5 and nutrient transporters in hepatocytes, which is related to chronic liver diseases.
非酒精性脂肪性肝病(NAFLD)在全球人群中的发病率高达 30%,可导致肝细胞癌(HCC),其 5 年相对生存率不到 40%。临床治疗策略并不十分成功。因此,在脂肪性肝炎的发展过程中,代谢紊乱和炎症环境的共同发生需要更具体地诊断和治疗,以防止致命的 HCC 发展。为了改善诊断和治疗策略,许多研究都探讨了鉴定与慢性肝病起始和进展相关的分子和/或途径,但仍需要进一步研究。已经观察到跨膜 4 L 六家族成员 5(TM4SF5)在体外细胞和体内动物模型中(以及没有或有 TM4SF5 表达的临床肝组织样本中)在调节肝细胞的代谢功能和活性方面发挥作用。TM4SF5 存在于不同细胞器或小泡的膜上,并与脂肪酸、氨基酸和单糖的转运蛋白合作,从而调节营养物质进入肝细胞的摄取和代谢,并导致慢性肝病的表型。此外,TM4SF5 可以通过在 TM4SF5 介导的慢性肝病期间与免疫细胞相互作用来重塑免疫环境。由于 TM4SF5 可能作为 NAFLD 的生物标志物,因此本综述总结了 TM4SF5 与肝细胞中营养物转运蛋白之间的相互作用,这与慢性肝病有关。