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. 2018 Oct 9;6:131. doi: 10.3389/fcell.2018.00131

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Copyright © 2018 Ireland and Mielgo.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Fibroblast activation. Quiescent fibroblasts produce few extracellular matrix (ECM) components such as fibronectin and collagen type 1 (Col1a1). They express fibroblasts specific protein-1 (FSP-1), actin and vimentin and secrete pigment epithelium-derived factor (PEDF) and thrombospondin-2 (THBS2). When stimulated with transforming growth factor beta (TGF-β), reactive oxygen species (ROS) or hypoxia, quiescent cells become activated increasing their contractility, proliferation and secretion. Activated myofibroblasts produce larger volumes of fibronectin and collagen along with tenascin-c and secreted protein acidic and rich in cysteine (SPARC). Increased secretion includes IL-6, tissue inhibitor of metalloproteinase (TIMPs), TGF-β, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and CXCL10. Upregulated receptors/markers include alpha smooth muscle actin (αSMA), platelet derived growth factor receptor alpha/beta (PDGFRα/β), fibroblast activation protein (FAP), discoidin domain-containing receptor 2 (DDR2), desmin, and vimentin.