Centre for Inflammation, Centenary Institute and University of Technology Sydney, Sydney, NSW, Australia.
Centre for Inflammation, Centenary Institute and University of Technology Sydney, Sydney, NSW, Australia; St Vincent's Medical School, UNSW Medicine, UNSW, Sydney, NSW, Australia.
Pharmacol Ther. 2021 Sep;225:107839. doi: 10.1016/j.pharmthera.2021.107839. Epub 2021 Mar 25.
Structural changes involving tissue remodelling and fibrosis are major features of many pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Abnormal deposition of extracellular matrix (ECM) proteins is a key factor in the development of tissue remodelling that results in symptoms and impaired lung function in these diseases. Tissue remodelling in the lungs is complex and differs between compartments. Some pathways are common but tissue remodelling around the airways and in the parenchyma have different morphologies. Hence it is critical to evaluate both common fibrotic pathways and those that are specific to different compartments; thereby expanding the understanding of the pathogenesis of fibrosis and remodelling in the airways and parenchyma in asthma, COPD and IPF with a view to developing therapeutic strategies for each. Here we review the current understanding of remodelling features and underlying mechanisms in these major respiratory diseases. The differences and similarities of remodelling are used to highlight potential common therapeutic targets and strategies. One central pathway in remodelling processes involves transforming growth factor (TGF)-β induced fibroblast activation and myofibroblast differentiation that increases ECM production. The current treatments and clinical trials targeting remodelling are described, as well as potential future directions. These endeavours are indicative of the renewed effort and optimism for drug discovery targeting tissue remodelling and fibrosis.
结构改变涉及组织重塑和纤维化是许多肺部疾病的主要特征，包括哮喘、慢性阻塞性肺疾病（COPD）和特发性肺纤维化（IPF）。细胞外基质（ECM）蛋白的异常沉积是组织重塑发展的一个关键因素，导致这些疾病出现症状和肺功能受损。肺部的组织重塑是复杂的，并且在不同的隔室之间存在差异。一些途径是共同的，但气道周围和实质中的组织重塑具有不同的形态。因此，评估共同的纤维化途径和特定于不同隔室的途径至关重要；从而扩展对哮喘、COPD 和 IPF 中气道和实质纤维化和重塑的发病机制的理解，以期为每种疾病开发治疗策略。在这里，我们回顾了这些主要呼吸系统疾病中重塑特征和潜在机制的最新认识。重塑的差异和相似之处用于突出潜在的共同治疗靶点和策略。重塑过程中的一个中心途径涉及转化生长因子（TGF）-β诱导的成纤维细胞激活和肌成纤维细胞分化，增加 ECM 的产生。描述了针对重塑的当前治疗方法和临床试验，以及潜在的未来方向。这些努力表明，针对组织重塑和纤维化的药物发现的努力和乐观情绪正在重新出现。
