Fibroblast Migration in Fibrosis

Fibroblast migration is a critical factor in wound healing, but also plays a fundamental role in fibrosis. For a fibroblast to migrate, the cell must be able to assemble factors that help it crawl across the extracellular matrix. Most of this movement is facilitated through the assembly and stability of the cytoskeleton that connects focal adhesion engagement with the extracellular matrix to intracellular stress fibers that wrap around the nucleus. These intracellular stress fibers help to polarize the fibroblast and orient the nucleus in the direction it is traveling. Changes in intracellular signaling for the fibroblast to move are also required, and this is necessitated by downstream signaling mediated by sonic hedgehog, WNT/β-catenin, ROCK/Rho, and PI3K/AKT. These changes regulate the stability of the cytoskeleton and, in addition, increase the expression of genes involved in cell migration. This review assimilates what is known about the function of the cytoskeleton in migration and the role of intracellular signaling pathways in fibrosis.