Hepatic stellate cells (HSCs) activation is a key step that promotes hepatic fibrosis. Emerging evidence suggests that aerobic glycolysis is one of its important metabolic characteristics. Our previous study has reported that CD147, a glycosylated transmembrane protein, contributes significantly to the activation of HSCs. However, whether and how it is involved in the aerobic glycolysis of HSCs activation is unknown. The objective of the present study was to validate the effect of CD147 in HSCs activation and the underlying molecular mechanism. Our results showed that the silencing of CD147 decreased the expression of α-smooth muscle-actin (α-SMA) and collagen I at both mRNA and protein levels. Furthermore, CD147 silencing decreased the glucose uptake, lactate production in HSCs, and repressed the lactate dehydrogenase (LDH) activity, the expression of hexokinase 2 (HK2), glucose transporter 1 (Glut1). The effect of galloflavin, a well-defined glycolysis inhibitor, was similar to CD147 siRNA. Mechanistically, CD147 silencing suppressed glycolysis-associated HSCs activation through inhibiting the hedgehog signaling. Moreover, the hedgehog signaling agonist SAG could rescue the above effect of CD147 silencing. In conclusion, CD147 silencing blockade of aerobic glycolysis via suppression of hedgehog signaling inhibited HSCs activation, suggesting CD147 as a novel therapeutic target for hepatic fibrosis.

肝星状细胞 (HSC) 激活是促进肝纤维化的关键步骤。新出现的证据表明，有氧糖酵解是其重要的代谢特征之一。我们之前的研究报告说，CD147 是一种糖基化的跨膜蛋白，对 HSC 的激活有显着贡献。然而，它是否以及如何参与 HSC 活化的有氧糖酵解尚不清楚。本研究的目的是验证 CD147 在 HSC 活化中的作用及其潜在的分子机制。我们的研究结果表明，CD147 的沉默降低了 α-平滑肌肌动蛋白 (α-SMA) 和胶原蛋白 I 在 mRNA 和蛋白质水平上的表达。此外，CD147 沉默降低了 HSC 中的葡萄糖摄取、乳酸产生，并抑制了乳酸脱氢酶 (LDH) 的活性，己糖激酶 2 (HK2)、葡萄糖转运蛋白 1 (Glut1) 的表达。没食子黄素是一种明确的糖酵解抑制剂，其作用类似于 CD147 siRNA。从机制上讲，CD147 沉默通过抑制刺猬信号来抑制糖酵解相关的 HSC 活化。此外，hedgehog 信号激动剂 SAG 可以挽救 CD147 沉默的上述作用。总之，CD147 通过抑制 Hedgehog 信号传导阻断有氧糖酵解抑制 HSC 活化，表明 CD147 是肝纤维化的新治疗靶点。刺猬信号激动剂 SAG 可以挽救 CD147 沉默的上述作用。总之，CD147 通过抑制 Hedgehog 信号传导阻断有氧糖酵解抑制 HSC 活化，表明 CD147 是肝纤维化的新治疗靶点。刺猬信号激动剂 SAG 可以挽救 CD147 沉默的上述作用。总之，CD147 通过抑制 Hedgehog 信号传导阻断有氧糖酵解抑制 HSC 活化，表明 CD147 是肝纤维化的新治疗靶点。