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.
Keyphrases
- idiopathic pulmonary fibrosis
- living cells
- endoplasmic reticulum
- fluorescent probe
- fluorescence imaging
- interstitial lung disease
- oxidative stress
- gene expression
- single molecule
- photodynamic therapy
- high resolution
- breast cancer cells
- small molecule
- metabolic syndrome
- drug delivery
- transcription factor
- cancer therapy
- climate change
- high glucose
- heat shock protein