TY - JOUR T1 - Uncovering colitis pre-symptomatic state as reflected by extracellular matrix compositional and structural signatures JF - bioRxiv DO - 10.1101/665653 SP - 665653 AU - Elee Shimshoni AU - Idan Adir AU - Ran Afik AU - Inna Solomonov AU - Anjana Shenoy AU - Miri Adler AU - Luca Puricelli AU - Veronica Ghini AU - Odelia Mouhadeb AU - Nathan Gluck AU - Sigal Fishman AU - Lael Werner AU - Dror S. Shouval AU - Chen Varol AU - Alessandro Podestà AU - Paola Turano AU - Tamar Geiger AU - Paolo Milani AU - Claudio Luchinat AU - Uri Alon AU - Irit Sagi Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/01/14/665653.abstract N2 - 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. ER -