DataSheet_4_Tanreqing Injection Attenuates Macrophage Activation and the Inflammatory Response via the lncRNA-SNHG1/HMGB1 Axis in Lipopolysaccharide-Induced Acute Lung Injury.xls

The etiology of acute lung injury (ALI) is not clear, and the treatment of ALI presents a great challenge. This study aimed to investigate the pathogenesis and potential therapeutic targets of ALI and to define the target gene of Tanreqing (TRQ), which is a traditional Chinese medicine formula composed of five medicines, scutellaria baicalensis, bear bile powder, goat horn powder, honeysuckle and forsythia. Macrophage activation plays a critical role in many pathophysiological processes, such as inflammation. Although the regulation of macrophage activation has been extensively investigated, there is little knowledge of the role of long noncoding RNAs (lncRNAs) in this process. In this study, we found that lncRNA-SNHG1 expression is distinctly regulated in differently activated macrophages in that it is upregulated in LPS. LncRNA-SNHG1 knockdown attenuates LPS-induced M1 macrophage activation. The SNHG1 promoter was bound by NF-κB subunit p65, indicative of SNHG1 being a direct transcriptional target of LPS-induced NF-κB activation. SNHG1 acts as a proinflammatory driver that leads to the production of inflammatory cytokines and the activation of macrophages and cytokine storms by physically interacting with high-mobility group box 1 (HMGB1) in ALI. TRQ inhibited NF-κB signaling activation and binding of NF-κB to the SNHG1 promoter. In conclusion, this study defined TRQ target genes, which can be further elucidated as mechanism(s) of TRQ action, and provides insight into the molecular pathogenesis of ALI. The lncRNA-SNHG1/HMGB1 axis is an ideal therapeutic for ALI treatment.

急性肺损伤（ALI）的病因尚不明确，其治疗亦面临重大挑战。本研究旨在探究ALI的发病机制及潜在治疗靶点，并确定传统中药方剂坦芩清（TRQ）的目标基因，该方剂由五味药材组成，包括黄芩、熊胆粉、羊角粉、金银花和连翘。巨噬细胞的活化在众多病理生理过程中扮演关键角色，如炎症反应。尽管巨噬细胞活化的调节机制已得到广泛研究，但关于长非编码RNA（lncRNA）在此过程中的作用知之甚少。在本研究中，我们发现lncRNA-SNHG1的表达在不同活化状态的巨噬细胞中存在显著差异，其在脂多糖（LPS）作用下呈上调。lncRNA-SNHG1的敲低可减轻LPS诱导的M1巨噬细胞活化。SNHG1启动子被NF-κB亚基p65结合，表明SNHG1是LPS诱导的NF-κB激活的直接转录靶点。SNHG1作为一种促炎驱动因子，通过与高迁移率族蛋白1（HMGB1）的物理相互作用，在ALI中导致炎症细胞因子的产生以及巨噬细胞和细胞因子风暴的激活。TRQ可抑制NF-κB信号通路激活及NF-κB与SNHG1启动子的结合。综上所述，本研究确定了TRQ的目标基因，这些基因可以进一步阐明TRQ的作用机制，并为ALI的分子发病机制提供了新的见解。lncRNA-SNHG1/HMGB1轴是ALI治疗的一个理想靶点。