Department of Respiratory Medicine , Binzhou Medical University Hospital , Binzhou 256603 , China.
Medicine Research Center, Institute of Molecular Medicine , Binzhou Medical University , Yantai 264003 , China.
Anal Chem. 2019 Apr 16;91(8):5424-5432. doi: 10.1021/acs.analchem.9b00713. Epub 2019 Mar 25.
Idiopathic pulmonary fibrosis (IPF) is a lung-limited and progressive fibrotic disease. The early diagnosis and therapies of IPF are still full of clinical challenges. Glutathione S-transferase (GSTs) plays significant roles in promoting the formation of pulmonary fibrosis. Herein, we report a fluorescent probe (Cy-GST) for the detection of GSTs concentration fluctuations in cells and in mice models. The probe can selectively and sensitively respond to GSTs with an "off-on" type fluorescence switch. Our results demonstrated that the level of intracellular GSTs increase in the pulmonary fibrosis cells and mice models. And the IPF patients hold high levels of GSTs concentrations. Thus, GSTs are likely to play important roles in pulmonary fibrosis. The inhibitor of GSTs TLK117 can reduce the severity of pulmonary fibrosis. The synergistic treatment of TLK117 and pirfenidone have better therapeutic effects than only using pirfenidone in pulmonary fibrosis mice models. The level of GSTs in IPF may be a new potential marker for IPF diagnosis. And the inhibition of GSTs may be a new therapeutic strategy for IPF treatment.
特发性肺纤维化（IPF）是一种肺部局限性、进行性纤维化疾病。IPF 的早期诊断和治疗仍然充满临床挑战。谷胱甘肽 S-转移酶（GSTs）在促进肺纤维化形成中发挥重要作用。在此，我们报告了一种用于检测细胞和小鼠模型中 GSTs 浓度波动的荧光探针（Cy-GST）。该探针可以选择性和灵敏地响应 GSTs，具有“关-开”型荧光开关。我们的结果表明，细胞内 GSTs 水平在肺纤维化细胞和小鼠模型中增加。并且 IPF 患者 GSTs 浓度较高。因此，GSTs 可能在肺纤维化中发挥重要作用。GSTs 的抑制剂 TLK117 可以减轻肺纤维化的严重程度。TLK117 和吡非尼酮的协同治疗在肺纤维化小鼠模型中的疗效优于仅使用吡非尼酮。IPF 中 GSTs 的水平可能是 IPF 诊断的一个新的潜在标志物。抑制 GSTs 可能是治疗 IPF 的一种新的治疗策略。
