11 General Introduction in fibrotic ECM mark the four neighboring regions with complex relationships with the realms of fibrotic ECM (Figure 1). “One Ring to rule them all, One Ring to find them, One Ring to bring them all, and in the darkness bind them.” – J.R.R. Tolkien. However, the details of the overruling capacity of ECM among the interactions between the ECM and the resident cells are still uncharted. By investigating and characterizing the interactions between the ECM and cells, which are already imprinted by the fibrotic ECM in vivo, we can broaden our horizons on how the pro-fibrotic cycle continues towards further activation of cells or disruption of composition, organization and mechanics of ECM. Figure 1: The landscape and influence of the Realms of Extracellular Matrix (ECM). Aberrant composition, disorganized fibers, altered biomechanics and abnormal cells are important areas that regulate the interactions between the (fibrotic) ECM and resident cells are shaped during the course of the fibrotic response. 1
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