Department of Forensic Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan.
Int J Mol Sci. 2023 Feb 5;24(4):3149. doi: 10.3390/ijms24043149.
Fibrosis and structural remodeling of the lung tissue can significantly impair lung function, often with fatal consequences. The etiology of pulmonary fibrosis (PF) is diverse and includes different triggers such as allergens, chemicals, radiation, and environmental particles. However, the cause of idiopathic PF (IPF), one of the most common forms of PF, remains unknown. Experimental models have been developed to study the mechanisms of PF, and the murine bleomycin (BLM) model has received the most attention. Epithelial injury, inflammation, epithelial-mesenchymal transition (EMT), myofibroblast activation, and repeated tissue injury are important initiators of fibrosis. In this review, we examined the common mechanisms of lung wound-healing responses after BLM-induced lung injury as well as the pathogenesis of the most common PF. A three-stage model of wound repair involving injury, inflammation, and repair is outlined. Dysregulation of one or more of these three phases has been reported in many cases of PF. We reviewed the literature investigating PF pathogenesis, and the role of cytokines, chemokines, growth factors, and matrix feeding in an animal model of BLM-induced PF.
肺组织的纤维化和结构重塑会显著损害肺功能，常导致致命后果。肺纤维化 (PF) 的病因多种多样，包括过敏原、化学物质、辐射和环境颗粒等不同的触发因素。然而，特发性 PF (IPF) 的病因仍不清楚，它是 PF 最常见的形式之一。已经开发了实验模型来研究 PF 的机制，其中鼠博来霉素 (BLM) 模型受到了最多的关注。上皮损伤、炎症、上皮-间充质转化 (EMT)、肌成纤维细胞激活和反复的组织损伤是纤维化的重要启动因素。在这篇综述中，我们检查了 BLM 诱导的肺损伤后肺愈合反应的常见机制以及最常见 PF 的发病机制。概述了一个涉及损伤、炎症和修复的三阶段伤口修复模型。在许多 PF 病例中，已经报道了这三个阶段中的一个或多个阶段的失调。我们综述了有关 PF 发病机制的文献，以及细胞因子、趋化因子、生长因子和基质在 BLM 诱导的 PF 动物模型中的作用。
