El-Merhie Natalia, Staab-Weijnitz Claudia A, Burgess Janette K, Kwapiszewska Grazyna
Institute for Lung Health (ILH), Cardiopulmonary Institute (CPI), Member of the German Center for Lung Research (DZL), Justus Liebig University, Giessen, Germany.
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Eur Respir Rev. 2025 Jul 23;34(177). doi: 10.1183/16000617.0192-2024. Print 2025 Jul.
Chronic lung diseases such as COPD, asthma, idiopathic pulmonary fibrosis (IPF) and pulmonary hypertension are characterised by aberrant remodelling and degradation of the extracellular matrix. This is particularly evident within the basement membrane. Collagen IV, a major component of the basement membrane, is essential for maintaining structural support and regulating cell behaviour. However, disruptions in collagen IV metabolism and basement membrane integrity have been implicated in the pathogenesis of chronic lung diseases, especially in ageing populations where basement membrane turnover is compromised. Cleavage of collagen IV during basement membrane remodelling generates bioactive fragments known as matrikines, which serve as markers of tissue remodelling and potential diagnostic biomarkers. Despite the prominence of collagen IV in the basement membrane, its role in chronic lung diseases remains understudied compared to other collagen types. This review provides a comprehensive exploration of the roles of basement membrane collagen IV and its matrikines in COPD, asthma, IPF and pulmonary hypertension, emphasising their significance beyond classical matrix components. Through an analysis of clinical studies, animal models and experiments, the contributions of collagen IV to disease pathogenesis and progression are discussed. Furthermore, potential diagnostic and therapeutic implications of targeting collagen IV are outlined. By providing insights into the relationship between collagen IV and chronic lung diseases, this review aims to guide future research and clinical interventions in the field.
慢性肺部疾病，如慢性阻塞性肺疾病（COPD）、哮喘、特发性肺纤维化（IPF）和肺动脉高压，其特征是细胞外基质的异常重塑和降解。这在基底膜中尤为明显。IV型胶原蛋白是基底膜的主要成分，对于维持结构支撑和调节细胞行为至关重要。然而，IV型胶原蛋白代谢和基底膜完整性的破坏与慢性肺部疾病的发病机制有关，尤其是在基底膜更新受损的老年人群中。基底膜重塑过程中IV型胶原蛋白的裂解会产生称为基质分子的生物活性片段，这些片段可作为组织重塑的标志物和潜在的诊断生物标志物。尽管IV型胶原蛋白在基底膜中很突出，但与其他类型的胶原蛋白相比，其在慢性肺部疾病中的作用仍未得到充分研究。本综述全面探讨了基底膜IV型胶原蛋白及其基质分子在COPD、哮喘、IPF和肺动脉高压中的作用，强调了它们超越经典基质成分的重要性。通过对临床研究、动物模型和实验的分析，讨论了IV型胶原蛋白对疾病发病机制和进展的贡献。此外，还概述了靶向IV型胶原蛋白的潜在诊断和治疗意义。通过深入了解IV型胶原蛋白与慢性肺部疾病之间的关系，本综述旨在指导该领域未来的研究和临床干预。
