Persistence of alveolar fibroblast-derived ADAMTS4+ cells in a preclinical model of delayed pulmonary fibrosis resolution
Year: 2026
Type: article
Abstract: Idiopathic pulmonary fibrosis is the most common and aggressive form of interstitial lung disease. Despite extensive research on the pathomechanisms of fibrogenesis, little is known about the mechanisms of fibrosis resolution. Here, lineage tracing of alveolar fibroblasts was carried out during fibrosis development and delayed resolution in aged mice. Histological analyses, single-cell transcriptomics, and ex vivo models including alveolar organoids and precision-cut lung slice cultures were employed. The data reveal that lipofibroblasts contribute to myofibroblast formation during fibrogenesis, with the reverse differentiation trajectory occurring during fibrosis resolution. Importantly, delayed resolution is associated with the persistence of ADAM metallopeptidase with thrombospondin type 1 motif 4-positive (ADAMTS4+) cells. Investigation of human lung transplant tissues, single-cell and spatial transcriptomic datasets, and functional ex vivo interventions reveal strong clinical relevance. Our study underscores the significance of the lipofibroblast-to-myofibroblast reversible switch in fibrosis development and resolution and identifies ADAM metallopeptidase with thrombospondin type 1 motif 4 as a potential therapeutic target in human lung fibrosis.
Source: Nature Communications
Authors: Mahsa Zabihi, Ali Khadim, Arun Lingampally, Ana Ivonne Vazquez-Armendariz, Stefan Hadzic, Georgios-Dimitrios Panagiotidis, Daniel Kalina, Jan Halweg, Tara Procida-Kowalski, Marek Bartkuhn, Xuran Chu, Janine Koepke, Christos Samakovlis, Mario Boehm, Norbert Weissmann, Andreas Günther, Werner Seeger, Peter Braubach, Susanne Herold, Malgorzata Wygrecka, Saverio Bellusci, Elie El Agha
Institutions: Justus-Liebig-Universität Gießen, German Center for Infection Research, German Center for Lung Research, Universities of Giessen and Marburg Lung Center, Cardio-Pulmonary Institute, University of Bonn, Wenzhou Medical University, Medizinische Hochschule Hannover, Quzhou City People's Hospital
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funder: Deutsche Forschungsgemeinschaft
OpenAlex ID: W7160646231