TY - JOUR T1 - Distinct extracellular-matrix remodeling events precede symptoms of inflammation 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/2020/03/27/665653.abstract N2 - Identification of early processes leading to complex tissue pathologies, such as inflammatory bowel diseases, poses a major scientific and clinical challenge that is imperative for improved diagnosis and treatment. Most studies of inflammation onset 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 dynamics during disease onset, while treating the matrix as a complete and defined entity. Through the analysis of matrix structure, stiffness and composition, we unexpectedly revealed that even prior to the first clinical symptoms, the colon displays its own unique extracellular-matrix signature and found specific markers of clinical potential, which were also validated in human subjects. We also show that the emergence of this pre-symptomatic matrix is mediated by sub-clinical infiltration of neutrophils and monocytes bearing remodeling enzymes. 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 -