The TGF-β1 Signaling Pathway as an Attractive Target in the Fibrosis Pathogenesis of Sjögren’s Syndrome

Figure 8

Schematic illustration of a working model for the TGF-β1/SMAD/Snail pathway in modulation of EMT-dependent fibrosis in SGEC. TGF-β1 stimulates epithelial cells by binding and activating transmembrane kinase receptors leading to phosphorylation and activation of Smad2/3. Once activated, pSmad2/3 form heterocomplexes with Smad4, which collectively translocate to the nucleus to mediate signaling events linked to EMT activation. The activation of the transcription factor Snail and induction of EMT markers have, as consequence, the upregulation of the mesenchymal marker Vimentin and the downregulation of the epithelial marker E-cadherin. During the activated EMT program, SGEC exhibit dramatic morphological changes and the gain of mesenchymal properties including increased migratory capacity and contractility. Finally, these mesenchymal cells become myofibroblasts which are responsible for progressive SG fibrosis.