PDF(Pubmed)
Abstract：
The circular RNA (circRNA) family is a group of endogenous non-coding RNAs (ncRNAs) that have critical functions in multiple physiological and pathological processes, including inflammation, cancer, and cardiovascular diseases. However, their roles in regulating innate immune responses remain unclear. Here, we define Cell division cycle 42 (CDC42)-165aa, a protein encoded by circRNA circCDC42, which is overexpressed in Klebsiella pneumoniae (KP)-infected alveolar macrophages. High levels of CDC42-165aa induces the hyperactivation of Pyrin inflammasomes and aggravates alveolar macrophage pyroptosis, while the inhibition of CDC42-165aa reduces lung injury in mice after KP infection by inhibiting Pyrin inflammasome-mediated pyroptosis. Overall, these results demonstrate that CDC42-165aa stimulates Pyrin inflammasome by inhibiting CDC42 GTPase activation and provides a potential clinical target for pathogenic bacterial infection in clinical practice.
摘要：
环状RNA（circularRNA，circRNA）家族是一组内源性非编码RNA（ncRNAs），在多种生理和病理过程中具有关键功能。包括炎症,癌症,和心血管疾病。然而,它们在调节先天免疫反应中的作用尚不清楚.这里,我们定义了细胞分裂周期42（CDC42）-165aa，一种由circRNAcircCDC42编码的蛋白质，在肺炎克雷伯菌（KP）感染的肺泡巨噬细胞中过表达。高水平的CDC42-165aa诱导了Pyrin炎性体的过度激活，并加重了肺泡巨噬细胞的焦亡，而抑制CDC42-165aa通过抑制Pyrin炎性体介导的细胞凋亡来减轻KP感染后小鼠的肺损伤。总的来说,这些结果表明,CDC42-165aa通过抑制CDC42GTP酶的激活而刺激Pyrin炎性体,为临床上的病原菌感染提供了一个潜在的临床靶点.
