急性肺损伤(ALI)是一种以急性低氧血症为特征的严重肺损伤,肺血管通透性增加,和炎症反应。尽管目前的治疗方法,ALI的死亡率仍然很高。这项研究发现,Sec13在ALI中高度表达,并通过糖酵解和上皮-间质转化(EMT)对其进行调节。在ALI小鼠模型和细胞模型中,Sec13表达增加,伴随着糖酵解的增强,EMT,和炎症。Sec13击倒抑制了这些影响,减轻阿里。Sec13与Pgm1形成蛋白质复合物,Pgm1是一种调节葡萄糖-6-磷酸(G6P)生产的酶,和ubqln1,一种泛素连接酶。Sec13抑制Ubqln1介导的PGM1泛素化,从而稳定Pgm1。在ALI,Pgm1与Sec13的结合增加,但与Ubqln1的结合减少。Sec13敲低降低乳酸,G6P,EMT标记,和炎性细胞因子。Pgm1敲低产生类似的效果。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中起关键作用,影响糖酵解和EMT。Sec13和Pgm1可能是治疗ALI的新靶点。
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.