title: Tissue remodelling in pulmonary fibrosis.
abstract: Many lung diseases result in fibrotic remodelling. Fibrotic lung disorders can be divided into diseases with known and unknown aetiology. Among those with unknown aetiology, idiopathic pulmonary fibrosis (IPF) is a common diagnosis. Because of its progressive character leading to a rapid decline in lung function, it is a fatal disease with poor prognosis and limited therapeutic options. Thus, IPF has motivated many studies in the last few decades in order to increase our mechanistic understanding of the pathogenesis of the disease. The current concept suggests an ongoing injury of the alveolar epithelium, an impaired regeneration capacity, alveolar collapse and, finally, a fibroproliferative response. The origin of lung injury remains elusive but a diversity of factors, which will be discussed in this article, has been shown to be associated with IPF. Alveolar epithelial type II (AE2) cells play a key role in lung fibrosis and their crucial role for epithelial regeneration, stabilisation of alveoli and interaction with fibroblasts, all known to be responsible for collagen deposition, will be illustrated. Whereas mechanisms of collagen deposition and fibroproliferation are the focus of many studies in the field, the awareness of other mechanisms in this disease is currently limited to biochemical and imaging studies including quantitative assessments of lung structure in IPF and animal models assigning alveolar collapse and collapse induration crucial roles for the degradation of the lung resulting in de-aeration and loss of surface area. Dysfunctional AE2 cells, instable alveoli and mechanical stress trigger remodelling that consists of collapsed alveoli absorbed by fibrotic tissue (i.e., collapse induration).
authors.affiliation: Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg Strasse 1, 30625, Hannover, Germany. Knudsen.lars@mh-hannover.de.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover Medical School, Hannover, Germany. Knudsen.lars@mh-hannover.de.|REBIRTH, Cluster of Excellence, Hannover Medical School, Hannover, Germany. Knudsen.lars@mh-hannover.de.
authors.forename: Lars
authors.initials: L
authors.lastname: Knudsen
authors.affiliation: Department of Internal Medicine, Justus-Liebig-University Giessen, Giessen, Germany.|Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Universities of Giessen and Marburg, Giessen, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Ruppert
authors.affiliation: Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg Strasse 1, 30625, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover Medical School, Hannover, Germany.|REBIRTH, Cluster of Excellence, Hannover Medical School, Hannover, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Ochs
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D018450:Disease Progression; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000473:pathology / Q000503:physiopathology*; D008954:Models, Biological; D011650:Pulmonary Alveoli / Q000473:pathology / Q000503:physiopathology; D013314:Stress, Mechanical
keywords: Alveolar collapse; Alveolar epithelial type 2 cells; Collapse induration; Idiopathic pulmonary fibrosis; Mechanical stress