Department of Hepatic Surgery and Liver Transplantation Center, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
Guangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
Dis Markers. 2023 Feb 16;2023:4352313. doi: 10.1155/2023/4352313. eCollection 2023.
With the intensification of population aging, the proportion of aging livers in the donor pool is increasing rapidly. Compared with young livers, aging livers are more susceptible to ischemia-reperfusion injury (IRI) during liver transplantation, which greatly affects the utilization rate of aging livers. The potential risk factors associated with IRI in aging livers have not been fully elucidated.
In this work, five human liver tissue expression profiling datasets (GSE61260, GSE107037, GSE89632, GSE133815, and GSE151648) and a total of 28 young and aging liver tissues of human ( = 20) and mouse ( = 8) were used to screen and verify the potential risk factors associated with aging livers being more prone to IRI. DrugBank Online was used to screen drugs with potential to alleviate IRI in aging livers.
The gene expression profile and immune cell composition between young and aging livers had significant differences. Among the differentially expressed genes, aryl hydrocarbon receptor nuclear translocator-like (ARNTL), BTG antiproliferation factor 2 (BTG2), C-X-C motif chemokine ligand 10 (CXCL10), chitinase 3-like 1 (CHI3L1), immediate early response 3 (IER3), Fos proto-oncogene, AP-1 transcription factor subunit (FOS), and peroxisome proliferative activated receptor, gamma, coactivator 1 alpha (PPARGC1A), mainly involved in the regulation of cell proliferation, metabolism, and inflammation, were also dysregulated in liver tissues suffered from IRI and could form a FOS-centered interaction network. Nadroparin was screened out with the potential to target FOS in DrugBank Online. In addition, the proportion of dendritic cells (DCs) was significantly upregulated in aging livers.
We combined the expression profiling datasets of liver tissues and samples collected in our hospital for the first time to reveal that the changes in the expression of ARNTL, BTG2, CXCL10, CHI3L1, IER3, FOS, and PPARGC1A and the proportion of dendritic cells may be associated with aging livers being more prone to IRI. Nadroparin may be used to mitigate IRI in aging livers by targeting FOS, and regulation of DC activity may also reduce IRI.
随着人口老龄化的加剧，供体池中老化肝脏的比例迅速增加。与年轻肝脏相比，衰老肝脏在肝移植过程中更容易发生缺血再灌注损伤（IRI），这极大地影响了衰老肝脏的利用率。与衰老肝脏 IRI 相关的潜在风险因素尚未得到充分阐明。
本研究使用五个人类肝脏组织表达谱数据集（GSE61260、GSE107037、GSE89632、GSE133815 和 GSE151648）和总共 28 个人类（n=20）和小鼠（n=8）的年轻和衰老肝脏组织，筛选和验证与衰老肝脏更容易发生 IRI 相关的潜在风险因素。使用 DrugBank Online 筛选具有缓解衰老肝脏 IRI 潜力的药物。
年轻和衰老肝脏之间的基因表达谱和免疫细胞组成存在显著差异。在差异表达基因中，芳香烃受体核转位蛋白样（ARNTL）、BTG 抗增殖因子 2（BTG2）、C-X-C 基序趋化因子配体 10（CXCL10）、几丁质酶 3 样 1（CHI3L1）、早期即刻反应 3（IER3）、Fos 原癌基因，AP-1 转录因子亚基（FOS）和过氧化物酶体增殖物激活受体，γ，共激活因子 1α（PPARGC1A）主要参与细胞增殖、代谢和炎症的调节，在遭受 IRI 的肝脏组织中也失调，并可形成以 FOS 为中心的相互作用网络。在 DrugBank Online 中筛选出具有靶向 FOS 潜力的那屈肝素。此外，在衰老肝脏中树突状细胞（DCs）的比例显著上调。
我们首次结合了肝脏组织的表达谱数据集和我们医院收集的样本，揭示了 ARNTL、BTG2、CXCL10、CHI3L1、IER3、FOS 和 PPARGC1A 的表达变化以及树突状细胞的比例可能与衰老肝脏更容易发生 IRI 有关。那屈肝素可能通过靶向 FOS 来减轻衰老肝脏的 IRI，而调节 DC 活性也可能减少 IRI。
