Cai Dasheng, Zhao Yue, Yu Fang
Department of Anesthesiology, the First Hospital of China Medical University, Shenyang, PR China.
Department of Anesthesiology, Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, PR China.
Cell Death Discov. 2022 Aug 18;8(1):368. doi: 10.1038/s41420-022-01137-8.
We commenced to analyze putative anti-pyroptosis effects of puerarin (PU) as mediated by the PP2A-HDAC1-NLRP3 pathway in acute lung injury (ALI). ALI animal and cell models were constructed, followed by treatment of PU. Then, the effect of HDAC1, PP2A, and NLRP3 on cell inflammation and pyroptosis was explored. The interaction between HDAC1 and PP2A as well as between PP2A and NLRP3 was analyzed. Our findings suggested that PU downregulated HDAC1 expression to alleviate symptoms of ALI. HDAC1 overexpression promoted inflammation induced by LPS, which reversed the inhibitory effect of PU on ALI. HDAC1 overexpression also decreased PP2A expression, suggesting that PP2A was involved in the effects of HDAC1 on LPS-induced inflammation. PP2A exerted inhibitory effects on NLRP3. Meanwhile, PU hindered the progression of ALI by silencing HDAC1 or overexpressing PP2A both in vivo and in vitro. Taken together, PU restrained pyroptosis of cells induced by NLRP3 inflammasome to abate ALI.
我们开始分析葛根素（PU）通过PP2A-HDAC1-NLRP3途径介导的对急性肺损伤（ALI）的潜在抗焦亡作用。构建了ALI动物和细胞模型，随后给予PU处理。然后，探究HDAC1、PP2A和NLRP3对细胞炎症和焦亡的影响。分析了HDAC1与PP2A之间以及PP2A与NLRP3之间的相互作用。我们的研究结果表明，PU下调HDAC1表达以减轻ALI症状。HDAC1过表达促进LPS诱导的炎症，这逆转了PU对ALI的抑制作用。HDAC1过表达还降低了PP2A表达，表明PP2A参与了HDAC1对LPS诱导炎症的作用。PP2A对NLRP3发挥抑制作用。同时，PU在体内和体外通过沉默HDAC1或过表达PP2A来阻碍ALI的进展。综上所述，PU抑制NLRP3炎性小体诱导的细胞焦亡以减轻ALI。
