Beyond classical collagen:basement membrane collagen IV in age-associated lung diseases

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 in vitro 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.