Year: 2026
Type: article
Abstract: The activation and accumulation of lung fibroblasts, leading to excessive ECM deposition, is a pathogenic hallmark of Idiopathic Pulmonary Fibrosis, a lethal and currently untreatable disease. In this report, increased expression of Versican, a multifunctional ECM proteoglycan, is detected in both human and mouse pulmonary fibrosis, mainly in monocytic cells and fibroblasts. Ubiquitous genetic reduction of Versican expression in mice promotes collagen expression and polymerisation, alters pulmonary ECM composition and structure, and exacerbates pulmonary fibrosis, delaying its resolution. Moreover, the decrease in Versican in the ECM and the ensuing reorganisation stimulate Tenascin-C expression from fibroblasts, which is further shown to be a potent Toll-like receptor 4-dependent podosome inducer, promoting ECM invasion. Thus, fibroblast-expressed Versican regulates the underlying ECM composition and structure and suppresses autologous podosome formation, limiting ECM invasion and pulmonary fibrosis. Idiopathic pulmonary fibrosis is characterised by the accumulation of fibroblasts, which deposit excessive extracellular matrix impairing respiratory functions. Here, the authors show that fibroblast-expressed versican, a chondroitin sulphate proteoglycan, suppresses fibroblasts’ ability to invade and further grow the underlying matrix, thus limiting their accumulation and attenuating pulmonary fibrosis.
Source: Nature Communications
Authors: Paraskevi Kanellopoulou, Ilianna Barbayianni, Dionysios Fanidis, Martina Samiotaki, Eleni Katsiouli, Dimitris Nastos, Stefanos Smyrniotis, Maria Shira, Apostolos Galaris, Vagelis Rinotas, Sofia Grammenoudi, Christiana Magkrioti, Ioannis Tomos, Africa Martinez Blanco, Ioanna Tremi, Ioannis Vamvakaris, Nuria Gavara, Sophia Havaki, Vassilis Gorgoulis, Hideto Watanabe, Vassilis Aidinis
Institutions: Alexander Fleming Biomedical Sciences Research Center, Universitat de Barcelona, National and Kapodistrian University of Athens, University of Dundee, Academy of Athens, Manchester Academic Health Science Centre, Ninewells Hospital, University of Surrey, University of Manchester, Biomedical Research Foundation of the Academy of Athens, Aichi Medical University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W7125099749