NHC Key Laboratory of Radiobiology, College of Public Health, Jilin University, Changchun 130021, China.
College of Animal Science, Jilin University, Changchun, Jilin 130062, China.
Int J Biol Macromol. 2023 Nov 1;251:126263. doi: 10.1016/j.ijbiomac.2023.126263. Epub 2023 Aug 9.
Liver fibrosis is a wound-healing response due to persistent liver damage and it may progress to cirrhosis and even liver cancer if no intervention is given. In the current cognition, liver fibrosis is reversible. So, it is of great significance to explore the related gene targets or biomarker for anti-fibrosis of liver. Insulin like growth factor 1 (IGF1) and IGF1 receptor (IGF1R) are mainly expressed in the liver tissues and play critical roles in the liver function. The present review summarized the role of IGF1/IGF1R and its signaling system in liver fibrosis and illustrated the potential mechanisms including DNA damage repair, cell senescence, lipid metabolism and oxidative stress that may be involved in this process according to the studies on the fibrosis of liver or other organs. In particular, the roles of IGF1 and IGF1R in DNA damage repair were elaborated, including membrane-localized and nucleus-localized IGF1R. In addition, for each of the potential mechanism in anti-fibrosis of liver, the signaling pathways of the IGF1/IGF1R mediated and the cell species in liver acted by IGF1 and IGF1R under different conditions were included. The data in this review will support for the study about the effect of IGF1/IGF1R on liver fibrosis induced by various factors, meanwhile, provide a basis for the study of liver fibrosis to focus on the communications between the different kinds of liver cells.
肝纤维化是一种持续性肝损伤导致的创伤愈合反应,如果不进行干预,它可能会进展为肝硬化,甚至肝癌。在目前的认知中,肝纤维化是可逆的。因此,探索肝纤维化的相关基因靶点或生物标志物具有重要意义。胰岛素样生长因子 1(IGF1)和 IGF1 受体(IGF1R)主要在肝组织中表达,在肝功能中发挥关键作用。本综述总结了 IGF1/IGF1R 及其信号系统在肝纤维化中的作用,并根据肝纤维化或其他器官纤维化的研究,阐述了可能涉及这一过程的潜在机制,包括 DNA 损伤修复、细胞衰老、脂质代谢和氧化应激。特别是,阐述了 IGF1 和 IGF1R 在 DNA 损伤修复中的作用,包括膜定位和核定位的 IGF1R。此外,对于肝纤维化的每一种潜在机制,都包括了 IGF1/IGF1R 介导的信号通路以及在不同条件下 IGF1 和 IGF1R 作用于肝内不同细胞类型的情况。本综述中的数据将支持 IGF1/IGF1R 对各种因素诱导的肝纤维化作用的研究,同时为肝纤维化的研究提供依据,以关注不同类型的肝细胞之间的通讯。