JQ1 is a potential therapeutic option for COPD patients with agrin overexpression
JQ1 is a potential therapeutic option for COPD patients with agrin overexpression
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JQ1 是 agrin 过度表达的 COPD 患者的潜在治疗选择
DOI：
10.1152/ajplung.00500.2017
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Han Yong
中科院分区：
文献类型：
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作者：
Xiao Zhen;Shu Jing;Zhou Feng;Han Yong
慢性阻塞性肺疾病（COPD）是全世界发病率和死亡的主要原因之一。它的特点是慢性肺部炎症和肺部气流受阻。迄今为止，尚无有效的慢性阻塞性肺病治疗方法。激活agn - yap通路可促进心脏再生。由于与ERBB2途径激活相比，agrin只能诱导轻微的心肌细胞增殖，因此它可能具有多效性，如减轻先天性炎症、免疫反应和纤维化。先前，我们证明了慢性阻塞性肺病和心力衰竭有几个共同的病理基因调控程序，如先天炎症和纤维化转录网络。在这项研究中，我们发现agrin与COPD的发生和进展呈负相关，并可能通过抑制先天炎症和纤维化信号通路发挥作用。BET抑制剂JQ1，与我们之前的研究结果一致，是治疗COPD患者的一种有希望的治疗选择。但在临床应用之前，还需要进行湿式实验室实验和临床试验。
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and death worldwide. It is characterized by chronic pulmonary inflammation and obstructed airflow from the lungs. To date, there is no effective treatment for COPD. The activation of the agrin (AGRN-YAP pathway can promote heart regeneration. Because agrin can induce only mild cardiomyocyte proliferation compared with ERBB2 pathway activation, it might exert pleiotropic effects, such as mitigation of innate inflammation, immune response, and fibrosis. Previously, we demonstrated that several common pathological gene regulatory programs such as innate inflammatory and profibrotic transcriptional networks were shared by COPD and heart failure. In this study, we show that agrin is inversely correlated with COPD development and progression and may exert its effects by suppressing innate inflammation and profibrotic signaling pathways. BET inhibitor JQ1, in line with our previous findings, is a promising therapeutic option in the treatment of patients with COPD. Nevertheless, wet laboratory experiments and clinical trials are needed before its application in clinical practice.