Li Qian, Gao Ling
Department of Pediatrics, Nanyang First People's Hospital, Nanyang, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):4265-4277. doi: 10.1007/s00210-024-03546-1. Epub 2024 Oct 24.
Asthma is one of the most common respiratory diseases in pediatric department. Several asthma-associated events including inflammatory responses, autophagy, and ferroptosis have been identified as typical pathological processes. TRIM7 is a member of TRIM proteins family associated with several types of diseases. Nevertheless, its role in asthma is still elusive. The current research showed that TRIM7 was involved in the pathogenesis of asthma mainly by regulating the Akt signaling pathway. In detail, we found that TRIM7 was highly expressed in patients with asthma and in an in vitro model of asthma. The following analysis indicated that TRIM7 knockdown attenuated the expression and secretion of inflammatory cytokines including TNF-α, IL-1β and IL-6 in lipopolysaccharide (LPS)-exposed human bronchial epithelial cells (HBECs). Meanwhile, knockdown of TRIM7 exerted inhibitory effects on LPS-induced autophagy and ferroptosis. Further mechanistic studies showed that TRIM7 knockdown inhibited LPS-induced activation of Akt pathway, while overexpression of Akt attenuated the inhibitory effects of TRIM7 knockdown on LPS-exposed HBECs. Collectively, we reported here that TRIM7 knockdown inhibited LPS-induced autophagy, ferroptosis, and inflammatory cytokine secretion in HBECs via regulating the Akt pathway, providing a new insight into the strategies for improving asthma treatments.
哮喘是儿科最常见的呼吸道疾病之一。包括炎症反应、自噬和铁死亡在内的几种与哮喘相关的事件已被确定为典型的病理过程。TRIM7是TRIM蛋白家族的成员，与多种疾病相关。然而，其在哮喘中的作用仍不清楚。目前的研究表明，TRIM7主要通过调节Akt信号通路参与哮喘的发病机制。具体而言，我们发现TRIM7在哮喘患者和哮喘体外模型中高表达。随后的分析表明，在脂多糖（LPS）刺激的人支气管上皮细胞（HBECs）中，敲低TRIM7可减弱包括TNF-α、IL-1β和IL-6在内的炎性细胞因子 的表达和分泌。同时，敲低TRIM7对LPS诱导的自噬和铁死亡具有抑制作用。进一步的机制研究表明，敲低TRIM7可抑制LPS诱导的Akt通路激活，而Akt的过表达可减弱敲低TRIM7对LPS刺激的HBECs的抑制作用。总的来说，我们在此报告，敲低TRIM7通过调节Akt通路抑制LPS诱导的HBECs自噬、铁死亡和炎性细胞因子分泌，为改善哮喘治疗策略提供了新的见解。
