Figure 1.

Schematic presentation of wound healing and fibrosis: (A) Cell death resulting from tissue injury results in recruitment of inflammatory cells through the damaged epithelium. These cells secrete proteases, degrade basement membrane, and release the components into circulation. Galectin-3 and TGF-β secreted by macrophages activate the resting fibroblasts into myofibroblasts, which secrete fresh basement membrane resulting in wound healing. The synthetic and degradative processes are in balance. (B) Constant and repetitive injury induces damage to the deeper interstitial layer and results in overproduction of the basement membrane components in an unorganized way leading to fibrosis. Secretion of IL-4 and IL-13 by inflammatory cells activates alternative macrophages, activated macrophages secrete increased galectin-3 and overexpress its cell surface receptor CD98. Galectin-3 and CD98 binding stabilizes CD98 and activates PI3K via an association with phosphorylated FAK and β-1 integrin. A galectin-3 feedback loop drives alternative macrophage activation. (Adapted from Genovese and Karsdal, 2016, Expert Review of Proteomics, 13 (2), 213–225).