Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
School of Basic Medical Science, Zhengzhou University, Zhengzhou, Henan, China.
Biochim Biophys Acta Mol Basis Dis. 2024 Dec;1870(8):167475. doi: 10.1016/j.bbadis.2024.167475. Epub 2024 Aug 17.
Acute lung injury (ALI) is a severe lung damage characterized by acute hypoxemia, increased pulmonary vascular permeability, and inflammatory reactions. Despite current treatments, mortality from ALI remains high. This study found that Sec13 is highly expressed in ALI and regulates it by glycolysis and epithelial-mesenchymal transition (EMT). In an ALI mouse model and cell model, Sec13 expression increased, accompanied by enhanced glycolysis, EMT, and inflammation. Sec13 knockdown suppressed these effects, alleviating ALI. Sec13 forms a protein complex with Pgm1, an enzyme regulating glucose-6-phosphate (G6P) production, and Ubqln1, an ubiquitin ligase. Sec13 inhibits Ubqln1-mediated Pgm1 ubiquitination, thereby stabilizing Pgm1. In ALI, Pgm1 binding to Sec13 increased but binding to Ubqln1 decreased. Sec13 knockdown decreased lactate, G6P, EMT markers, and inflammatory cytokines. Pgm1 knockdown produced similar effects. Ubqln1 overexpression suppressed inflammation but decreased Pgm1 expression. In conclusion, Sec13 plays a key role in ALI by inhibiting Ubqln1-mediated Pgm1 ubiquitination, affecting glycolysis and EMT. Sec13 and Pgm1 may be new targets for treating ALI.
急性肺损伤 (ALI) 是一种严重的肺部损伤，其特征为急性低氧血症、肺血管通透性增加和炎症反应。尽管目前有治疗方法，但 ALI 的死亡率仍然很高。本研究发现 Sec13 在 ALI 中高度表达，并通过糖酵解和上皮-间充质转化 (EMT) 来调节它。在 ALI 小鼠模型和细胞模型中，Sec13 的表达增加，伴随着糖酵解、EMT 和炎症的增强。Sec13 敲低抑制了这些作用，缓解了 ALI。Sec13 与 Pgm1（一种调节葡萄糖-6-磷酸 (G6P) 生成的酶）和 Ubqln1（一种泛素连接酶）形成蛋白复合物。Sec13 抑制 Ubqln1 介导的 Pgm1 泛素化，从而稳定 Pgm1。在 ALI 中，Pgm1 与 Sec13 的结合增加，但与 Ubqln1 的结合减少。Sec13 敲低减少了乳酸、G6P、EMT 标志物和炎症细胞因子。Pgm1 敲低产生了类似的效果。Ubqln1 过表达抑制了炎症，但降低了 Pgm1 的表达。总之，Sec13 通过抑制 Ubqln1 介导的 Pgm1 泛素化在 ALI 中发挥关键作用，影响糖酵解和 EMT。Sec13 和 Pgm1 可能是治疗 ALI 的新靶点。
