Fig. 4

Gal-1- and Gal-3 pathways promoting EMT in fibrosis. (a) Gal-1 promotes lung and sub-retinal fibrosis involving activation of a FAK/TGFR-β/Smad pathway, which in turn induces Gal-1 expression as positive feedback and is counteracted by Gal-1 inhibitor OTX008. This pathway most likely includes activation of β1-integrins upstream FAK. Intracellular Gal-1 interacts with FAK1 suggesting an additional intracellular unknown role. Indeed, TGFR-β/Smad can be directly stimulated by TGF-β with similar effects. In retinal epithelial cells Gal-1 activates VEGFR2-ERK to promote subretinal fibrosis (b) or can enhance the EMT phenotype induced by TGF-β/Smad signaling (c). (d) Gal-1 expression is enhanced in a cellular model of diabetic retinopathy promoting EMT-associated fibrosis through an unknown mechanism, which can be blocked by OTX008. Gal-3 interacts with TGF-βR contributing to the TGF-β1-induced EMT involved in lung and renal fibrosis. The pathway includes β-catenin and can be blocked by Gal-3 inhibitors TD139 (e) and MCP (f)