Metabolic reprogramming plays a critical role in many diseases. A recent study revealed that aerobic glycolysis in lung tissue is closely related to pulmonary fibrosis, and also occurs during lipopolysaccharide (LPS)-induced sepsis. However, whether LPS induces aerobic glycolysis in lung fibroblasts remains unknown. The present study demonstrated that LPS promotes collagen synthesis in the lung fibroblasts through aerobic glycolysis via the activation of the PI3K-Akt-mTOR/PFKFB3 pathway. Challenging the human lung fibroblast MRC-5 cell line with LPS activated the PI3K-Akt-mTOR pathway, significantly upregulated the expression of 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3), enhanced the aerobic glycolysis, and promoted collagen synthesis. These phenomena could be reversed by the PI3K-Akt inhibitor LY294002, mTOR inhibitor rapamycin, PFKFB3 inhibitor 3PO, or PFKFB3 silencing by specific shRNA, or aerobic glycolysis inhibitor 2-DG. In addition, PFKFB3 expression and aerobic glycolysis were also detected in the mouse model of LPS-induced pulmonary fibrosis, which could be reversed by the intraperitoneal injection of PFKFB3 inhibitor 3PO. Taken together, this study revealed that in LPS-induced pulmonary fibrosis, LPS might mediate lung fibroblast aerobic glycolysis through the activation of the PI3K-Akt-mTOR/PFKFB3 pathway.

代谢重编程在许多疾病中起着关键作用。最近的一项研究表明，肺组织中的有氧糖酵解与肺纤维化密切相关，并且在脂多糖 (LPS) 诱导的败血症期间也会发生。然而，LPS 是否在肺成纤维细胞中诱导有氧糖酵解仍然未知。本研究表明，LPS 通过激活 PI3K-Akt-mTOR/PFKFB3 通路，通过有氧糖酵解促进肺成纤维细胞中的胶原蛋白合成。用 LPS 挑战人肺成纤维细胞 MRC-5 细胞系激活 PI3K-Akt-mTOR 通路，显着上调 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) 的表达，增强有氧糖酵解, 并促进胶原蛋白的合成。这些现象可以被 PI3K-Akt 抑制剂 LY294002 逆转，mTOR 抑制剂雷帕霉素、PFKFB3 抑制剂 3PO 或通过特定 shRNA 或有氧糖酵解抑制剂 2-DG 沉默的 PFKFB3。此外，在 LPS 诱导的肺纤维化小鼠模型中也检测到 PFKFB3 表达和有氧糖酵解，这可以通过腹腔注射 PFKFB3 抑制剂 3PO 来逆转。总之，这项研究表明，在 LPS 诱导的肺纤维化中，LPS 可能通过激活 PI3K-Akt-mTOR/PFKFB3 通路介导肺成纤维细胞有氧糖酵解。