Idiopathic pulmonary fibrosis (IPF) has been characterized as a chronic inflammatory disease that leads to irreversible damage to pulmonary function. However, there is no specific IPF biomarker that can be used to distinguish IPF and not pneumonia. Endoplasmic reticulum (ER) stress is prominent in IPF. To search for a specific biomarker of IPF, we developed two ER-targeting two-photon (TP) fluorescent probes, TP^ER-ONOO and TP^ER-Cys, for peroxynitrite (ONOO^–) and cysteine (Cys) imaging, respectively. A significant increase in Cys levels in the lungs was discovered only in mice with IPF, which implied that Cys might be an IPF biomarker candidate. Furthermore, we uncovered the mechanism of glutathione (GSH) deficiency in IPF, which was not due to Cys shortage but instead was attributable to impaired glutamate cysteine ligase and glutathione synthetase activities via ONOO^–-induced post-transcriptional modification. This work has potential to provide a new method for IPF early diagnosis and drug efficacy evaluation.

中文翻译：

---

通过半胱氨酸和过氧亚硝酸盐的同时双光子荧光成像探索特发性肺纤维化生物标志物

特发性肺纤维化 (IPF) 已被描述为一种慢性炎症性疾病，可导致肺功能不可逆的损害。然而，没有特定的 IPF 生物标志物可用于区分 IPF 和肺炎。内质网 (ER) 应激在 IPF 中尤为突出。^{为了寻找 IPF 的特定生物标志物，}我们开发了两种针对过氧亚^硝酸盐（^ONOO-) 和半胱氨酸 (Cys) 成像，分别。仅在患有 IPF 的小鼠中发现了肺中 Cys 水平的显着增加，这意味着 Cys 可能是 IPF 生物标志物的候选者。此外，我们揭示了 IPF 中谷胱甘肽 (GSH) 缺乏的机制，这不是由于 Cys 缺乏，而是由于ONOO诱导^的转录后修饰导致谷氨酸半胱氨酸连接酶和谷胱甘肽合成酶活性受损。这项工作有可能为IPF早期诊断和药效评价提供一种新方法。