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The extracellular matrix (ECM) is the common denominator of more than 50 chronic diseases. Some of these chronic pathologies lead to enhanced tissue formation and deposition, whereas others are associated with increased tissue degradation, and some exhibit a combination of both, leading to severe tissue alterations. To develop effective therapies for diseases affecting the lung, liver, kidney, skin, intestine, musculoskeletal system, heart, and solid tumors, we need to modulate the ECM’s composition to restore its organization and function. Across diverse organ diseases, there are common denominators and distinguishing factors in this fibroinflammatory axis, which may be used to foster new insights into drug development across disease indications. The 2nd Extracellular Matrix Pharmacology Congress took place in Copenhagen, Denmark, from 17 to 19 June 2024 and was hosted by the International Society of Extracellular Matrix Pharmacology. The event was attended by 450 participants from 35 countries, among whom were prominent scientists who brought together state-of-the-art research on organ diseases and asked important questions to facilitate drug development. We highlight key aspects of the ECM in the liver, kidney, skin, intestine, musculoskeletal system, lungs, and solid tumors to advance our understanding of the ECM and its central targets in drug development. We also highlight key advances in the tools and technology that enable this drug development, thereby supporting the ECM.

IL11 is linked to the pathogenesis of idiopathic pulmonary fibrosis (IPF), since IL11 induces myofibroblast differentiation and stimulates their excessive collagen deposition in the lung. The alveolar architecture is disrupted in IPF, yet the effect of IL11 on dysregulated alveolar repair associated with IPF remains to be elucidated. We hypothesized that epithelial-fibroblast communication associated with lung repair is disrupted by IL11. Thus, we studied whether IL11 affects the repair responses of alveolar lung epithelium using mouse lung organoids and precision cut lung slices (PCLS). Additionally, we assessed the anatomical distribution of IL11 and IL11 receptor in human control and IPF lungs using immunohistochemistry. IL11 protein was observed in human control lungs in airway epithelium, macrophages and in IPF lungs, in areas of AT2 cell hyperplasia. IL11R staining was predominantly present in smooth muscle and macrophages. In mouse organoid cocultures of epithelial cells with lung fibroblasts, IL11 decreased organoid number and reduced the fraction of pro-SPC expressing organoids, indicating dysfunctional regeneration initiated by epithelial progenitors. In mouse PCLS alveolar marker gene expression declined, whereas airway markers were increased. The response of primary human fibroblasts to IL11 on gene expression level was minimal, though bulk RNAsequencing revealed IL11 modulated a number of processes which may play a role in IPF, including unfolded protein response, glycolysis and Notch signaling. In conclusion, IL11 disrupts alveolar epithelial regeneration by inhibiting progenitor activation and suppressing the formation of mature alveolar epithelial cells. The contribution of dysregulated fibroblast epithelial communication to this process appears to be limited.Competing Interest StatementThis research was supported by an unrestricted research grant from Boehringer Ingelheim to the University of Groningen. Kerstin E. Geillinger-Kaestle and Megan Webster were employed by Boehringer Ingelheim when contributing to this manuscript.Footnotes* Supplemental files updated