Fibroblast—Extracellular Matrix Interactions in Tissue Fibrosis

Activated myofibroblasts are key effector cells in tissue fibrosis. Emerging evidence suggests that myofibroblasts infiltrating fibrotic tissues originate predominantly from local mesenchyme-derived populations. Alterations in the extracellular matrix network play an important role in modulating fibroblast phenotype and function. In a pro-inflammatory environment, generation of matrix fragments may induce a matrix-degrading fibroblast phenotype. Deposition of ED-A fibronectin plays an important role in myofibroblast transdifferentiation. In fibrotic tissues, the matrix is enriched with matricellular macromolecules that regulate growth factor-mediated responses and modulate protease activation. This manuscript discusses emerging concepts on the role of the extracellular matrix in regulation of fibroblast behavior.