Figure 7.

Schematic conclusion of data. DSG2 (desmoglein-2) –W2A mutation with loss of desmosomal adhesion leads to impaired intercalated disc (ICD) structure with deregulation of integrin-β6 (ITGB6) and enhanced heterodimerization with integrin-αV (ITGAV). The dimer efficiently binds to the extracellular matrix and activates transforming growth factor–β (TGF-β) by removal of the latency-associated peptide (LAP). Active TGF-β can then induce profibrotic downstream signaling by means of SMAD molecules. In our experiments, this cascade was blocked by different approaches to inhibit ITGAV/B6.