Li Zhongzheng, Zhang Mengke, Zhang Yujie, Gan Yulong, Zhu Zhao, Wang Jiawei, Zhou Yanlin, Yu Guoying, Wang Lan
State Key Laboratory of Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Organ Fibrosis, Pingyuan Laboratory, College of Life Science, Henan Normal University, 46 Jianshe Road, Xinxiang, Henan, 453007, China.
Epigenetics Chromatin. 2025 Mar 12;18(1):11. doi: 10.1186/s13072-025-00579-5.
Pulmonary fibrosis is a relentless and ultimately fatal lung disorder. Despite a wealth of research, the intricate molecular pathways that contribute to the onset of PF, especially the aspects related to epigenetic modifications and chromatin dynamics, continue to be elusive and not fully understood.
Utilizing a bleomycin-induced pulmonary fibrosis model, we conducted a comprehensive analysis of the interplay between chromatin structure, chromatin accessibility, gene expression patterns, and cellular heterogeneity. Our chromatin structure analysis included 5 samples (2 control and 3 bleomycin-treated), while accessibility and expression analysis included 6 samples each (3 control and 3 bleomycin-treated).
We found that chromatin architecture, with its alterations in compartmentalization and accessibility, is positively correlated with genome-wide gene expression changes during fibrosis. The importance of immune system inflammation and extracellular matrix reorganization in fibrosis is underscored by these chromatin alterations. Transcription factors such as PU.1, AP-1, and IRF proteins, which are pivotal in immune regulation, are associated with an increased abundance of their motifs in accessible genomic regions and are correlated with highly expressed genes.
We identified 14 genes that demonstrated consistent changes in their expression, accessibility, and compartmentalization, suggesting their potential as promising targets for the development of treatments for lung fibrosis.
肺纤维化是一种持续进展且最终致命的肺部疾病。尽管进行了大量研究，但导致肺纤维化发病的复杂分子途径，尤其是与表观遗传修饰和染色质动态变化相关的方面，仍然难以捉摸且尚未完全理解。
利用博来霉素诱导的肺纤维化模型，我们对染色质结构、染色质可及性、基因表达模式和细胞异质性之间的相互作用进行了全面分析。我们的染色质结构分析包括5个样本（2个对照和3个博来霉素处理组），而可及性和表达分析各包括6个样本（3个对照和3个博来霉素处理组）。
我们发现，染色质结构及其在分隔和可及性方面的改变与纤维化过程中全基因组基因表达变化呈正相关。这些染色质改变突出了免疫系统炎症和细胞外基质重组在纤维化中的重要性。在免疫调节中起关键作用的转录因子，如PU.1、AP-1和IRF蛋白，与它们在可及基因组区域基序丰度的增加相关，并与高表达基因相关。
我们鉴定出14个基因，其表达、可及性和分隔表现出一致变化，表明它们有望成为肺纤维化治疗开发的靶点。
