Abstract
Tissue damage, manifesting in the extracellular matrix, is a hallmark of inflammatory bowel disease progression and severity. Nevertheless, most studies focus on cellular processes and signaling molecules, while overlooking the environment in which they take place, the continuously remodeled extracellular matrix. In this study, we used colitis models for investigating extracellular-matrix remodeling dynamics during disease onset. We reveal that even prior to the first inflammatory symptoms, the colon displays a unique extracellular-matrix signature in terms of composition, morphology and stiffness. Specifically, the matrix becomes perforated at pre-symptomatic states, which is mediated by sub-clinical infiltration of neutrophils and monocytes bearing remodeling enzymes. The unique proteomic composition of this newly discovered state is also marked by specific biomarkers. Remarkably, whether the inflammation is chronic or acute, its matrix signature converges at pre-symptomatic states. We suggest that the existence of a pre-symptomatic extracellular-matrix is general and relevant to a wide range of diseases.