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Publication : Distinct extracellular-matrix remodeling events precede symptoms of inflammation.

First Author  Shimshoni E Year  2021
Journal  Matrix Biol Volume  96
Pages  47-68 PubMed ID  33246101
Mgi Jnum  J:316352 Mgi Id  MGI:6709847
Doi  10.1016/j.matbio.2020.11.001 Citation  Shimshoni E, et al. (2021) Distinct extracellular-matrix remodeling events precede symptoms of inflammation. Matrix Biol 96:47-68
abstractText  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 subclinical infiltration of immune cells 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.
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