Gao Lili, Wang Nan, Jiang Yu, Hu Jinying, Ma Baojie, Wu Taihua
Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
Department of Anesthesia, Dalian Women and Children's Medical Group, Dalian 116000, China.
Evid Based Complement Alternat Med. 2022 Jul 6;2022:5943322. doi: 10.1155/2022/5943322. eCollection 2022.
Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable chronic interstitial lung disease with an unknown etiology. Recent evidence suggests that epithelial-mesenchymal transition (EMT) is one of the possible factors in the pathogenesis of pulmonary fibrosis. Glycyrrhizic acid (GA) is a natural active ingredient extracted from the root of the traditional Chinese herb licorice, which has been shown in previous studies to have the effect of alleviating lung injury. In this study, our objective was to investigate whether GA could ameliorate pulmonary fibrosis by altering EMT, as well as the therapeutic potential of changing core fucosylation (CF) to target EMT-related pathways. First, we verified that GA partially reverses EMT in a rat model of bleomycin-induced lung interstitial fibrosis, alleviating pulmonary fibrosis, and implying that GA has antifibrotic potential. Next, we discovered that GA attenuated lung interstitial fibrosis by reducing CF modifications to some extent. Interestingly, we found that GA therapy reduced the expression of phosphorylated Smad2/3 (p-Smad2/3) and -catenin in the EMT pathway and that GA inhibited the modification of TGF-R and WNT receptor proteins by CF, suggesting that GA may interfere with the EMT process by modulating TGF-R, WNT core fucosylation modifications to attenuate pulmonary fibrosis. In conclusion, these findings indicate that GA could be a potential therapeutic agent for IPF, and further support the idea that targeting CF alterations could be a novel technique for the treatment of diseases involving EMT.
特发性肺纤维化（IPF）是一种病因不明的致命且无法治愈的慢性间质性肺疾病。最近的证据表明，上皮-间质转化（EMT）是肺纤维化发病机制中的可能因素之一。甘草酸（GA）是从传统中药甘草根部提取的天然活性成分，先前的研究表明其具有减轻肺损伤的作用。在本研究中，我们的目的是探讨GA是否可以通过改变EMT来改善肺纤维化，以及改变核心岩藻糖基化（CF）以靶向EMT相关途径的治疗潜力。首先，我们证实GA在博来霉素诱导的大鼠肺间质纤维化模型中部分逆转EMT，减轻肺纤维化，这意味着GA具有抗纤维化潜力。接下来，我们发现GA在一定程度上通过减少CF修饰来减轻肺间质纤维化。有趣的是，我们发现GA治疗降低了EMT途径中磷酸化Smad2/3（p-Smad2/3）和β-连环蛋白的表达，并且GA抑制了CF对TGF-βR和WNT受体蛋白的修饰，这表明GA可能通过调节TGF-βR、WNT核心岩藻糖基化修饰来干扰EMT过程，从而减轻肺纤维化。总之，这些发现表明GA可能是IPF的潜在治疗药物，并进一步支持靶向CF改变可能是治疗涉及EMT疾病的新技术这一观点。
