Early Detection of Urinary Proteome Biomarkers for Effective Early Treatment of Pulmonary Fibrosis in a Rat Model

Scope: Pulmonary fibrosis (PF) is a progressive and devastating lung disease. With limited effective treatments available in the late stage, PF has a very poor prognosis. Molecular biomarkers are highly desired for PF, especially for its early phase. Materials and methods: Urine is a good biomarker source, and accumulates systemic changes in the body especially in the early-stage of diseases. In this study, a bleomycin (BLM)-induced rat model is used to mimic PF. Using labeled proteome quantitation, some urinary proteins are identified as candidate biomarkers of PF for early detection and disease monitoring. Then, prednisone treatment is administered at different phases of fibrosis. Results: Our results suggested that urine proteins could enable early detection and monitoring of both disease progression and treatment efficacy in the BLM-induced PF model. Early prednisone treatment effectively inhibited pulmonary fibrosis, whereas the same treatment at a later phase had very limited effects. Meanwhile, five proteins showed the potential for monitoring therapeutic response. Conclusion: Urinary proteomics has been underutilized in respiratory diseases. These findings will improve our understanding of the pathogenesis of PF and accelerate biomarker discovery in respiratory diseases.