Intracellular hydroxyproline imprinting following resolution of bleomycin-induced pulmonary fibrosis

作者：Shengren Song, Zhenli Fu, Ruijuan Guan, Jie Zhao, Penghui Yang, Yang Li, Hang Yin, Yunxin Lai, Gencheng Gong, Simin Zhao, Jiangtian Yu, Xiaomin Peng, Ying He, Yumei Luo, Nanshan Zhong, Jin Su · 发表于：European Respiratory Journal · 年份：2021 · DOI：10.1183/13993003.00864-2021 · 被引用次数：113 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Proteoglycans and glycosaminoglycans research、Pleural and Pulmonary Diseases

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with few treatment options. The poor success in developing anti-IPF strategies has impelled researchers to reconsider the importance of the choice of animal model and assessment methodologies. Currently, it is still not settled whether the bleomycin-induced lung fibrosis mouse model finally returns to resolution. METHODS: This study aimed to follow the dynamic fibrotic features of bleomycin-treated mouse lungs over extended durations through a combination of the latest technologies (micro-computed tomography imaging and histological detection of degraded collagens) and traditional methods. In addition, we also applied immunohistochemistry to explore the distribution of all hydroxyproline-containing molecules. RESULTS: As determined by classical biochemical methods, total lung hydroxyproline contents reached a peak at 4 weeks after bleomycin injury and maintained a steady high level thereafter until the end of the experiments (16 weeks). This result seemed to partially contradict with the changes of other fibrosis evaluation parameters, which indicated a gradual degradation of collagens and a recovery of lung aeration after the fibrosis peak. This inconsistency was well reconciled by our data from immunostaining against hydroxyproline and fluorescent peptide staining against degraded collagen, together showing large amounts of hydroxyproline-rich degraded collagen fragments detained and enriched within the...