Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei 430060, China.
Chin Med J (Engl). 2022 Dec 5;135(23):2859-2868. doi: 10.1097/CM9.0000000000002540.
Sepsis is a systemic inflammatory syndrome induced by several infectious agents. Multiple organs are affected by sepsis, including the liver, which plays an important role in metabolism and immune homeostasis. Fibroblast growth factors (FGFs) participate in several biological processes, although the role of FGF5 in sepsis is unclear.
In this study, lipopolysaccharide (LPS) was administrated to mice to establish a sepsis-induced liver injury. A similar in vitro study was conducted using L-02 hepatocytes. Western blot and immunohistochemistry staining were performed to evaluate the FGF5 expression level in liver tissues and cells. Inflammatory cell infiltrations, cleaved-caspase-3 expressions, reactive oxygen species and levels of inflammatory cytokines were detected by immunofluorescence, dihydroethidium staining, and reverse transcription quantitative polymerase chain reaction analysis, respectively. Flow cytometry was used to detect the apoptosis level of cells. In addition, ribonucleic acid (RNA)-sequencing was applied to explore the possible mechanism by which FGF5 exerted effects.
LPS administration caused FGF5 down-regulation in the mouse liver as well as in L-02 hepatocytes. Additionally, with FGF5 overexpression, liver injury and the level of hepatocyte apoptosis were ameliorated. Further, RNA sequencing performed in hepatocytes revealed the phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) pathway as a possible pathway regulated by FGF5 . This was supported using an inhibitor of the PI3K/AKT pathway, which abrogated the protective effect of FGF5 in LPS-induced hepatocyte injury.
The anti-apoptotic effect of FGF5 on hepatocytes suffering from LPS has been demonstrated and was dependent on the activation of the PI3K/AKT signaling pathway.
败血症是由多种感染因子引起的系统性炎症综合征。多个器官受到败血症的影响，包括肝脏，肝脏在代谢和免疫平衡中起着重要作用。成纤维细胞生长因子（FGFs）参与了多种生物学过程，尽管 FGF5 在败血症中的作用尚不清楚。
在这项研究中，给小鼠注射脂多糖（LPS）以建立败血症诱导的肝损伤模型。在体外使用 L-02 肝细胞进行了类似的研究。采用 Western blot 和免疫组织化学染色法检测肝组织和细胞中 FGF5 的表达水平。通过免疫荧光、二氢乙啶染色、逆转录定量聚合酶链反应分析分别检测炎性细胞浸润、半胱天冬酶-3 表达、活性氧和炎症细胞因子水平。流式细胞术用于检测细胞凋亡水平。此外，还应用 RNA 测序探讨 FGF5 发挥作用的可能机制。
LPS 给药导致小鼠肝脏以及 L-02 肝细胞中 FGF5 下调。此外，过表达 FGF5 可改善肝损伤和肝细胞凋亡水平。进一步在肝细胞中进行的 RNA 测序显示，磷酸肌醇 3-激酶/蛋白激酶 B（PI3K/AKT）通路可能是 FGF5 调节的通路。使用 PI3K/AKT 通路抑制剂证实了这一点，该抑制剂消除了 FGF5 对 LPS 诱导的肝细胞损伤的保护作用。
已经证明 FGF5 对 LPS 作用下的肝细胞具有抗凋亡作用，并且这种作用依赖于 PI3K/AKT 信号通路的激活。
