Fig. 2.

Schematic representation of the mechanism regulating myofibroblasts activation in pulmonaryl fibrosis (PF). Soluble mediators such as tumor growth factor–β (TGF-β), interleukin-6 (IL-6), and galectin-3 (Gal-3) promote the transformation of endothelial cells to myofibroblasts (EndMT). Similarly, TGF-β, and IL-6 favour the epithelial-mesenchymal transition (EMT) of alveolar endothelial type 1 (AT1) cells. Another source of myofibroblasts derives from the activation of resident fibroblast and pericytes by TGF-β, the platelet-derived growth factor (PDGF) and fibroblast growth factor 2 (FGF-2) in a process defined fibroblast to myofibroblast transformation (FMT). The activation of TGF-β signalling promotes the formation of myofibroblast from lipofibroblasts. Despite the activation of the peroxisome proliferator-activated receptors-gamma (PPARγ) signalling that could counteract the myofibroblast activation, these pathways are downregulated in PF. The release of IL-8 can also drive the activation of mesenchymal stromal cells (MSCs). The increase of myofibroblast cell bulk causes the over-production of extracellular matrix (ECM).