Fig. 4

Ingenuity Pathway Analysis showing the plasma membrane and extracellular proteins directly related to YAP1. The relation to proteins involved in mechanotransduction include the cell membrane protein PATJ (crumbs cell polarity complex component), which is directly related to YAP1 and is also interacting with PIEZO1, the Piezo type mechanosensitive ion channel component 1. YAP1 is also an indirect regulator of both PIEZO1 and PIEZO2. Further, the cytokine endothelin 1 (EDN1) is directly related to YAP1 and is also a regulator of the degenerin/epithelial sodium channels (DEG/ENaC, here marked as SCNN1A, SCNN1B, SCNN1G, SCNN1D). Tight junction signaling proteins related to YAP1 include CTNNA1, MPDZMPP5, OCLN, PATJ, TJP2. Epithelial adherens junction signaling proteins related to YAP1 include CDH1, CTNNA1, CTNNA2, EGFR, FGF1, PARD3, ZYX. Examples of secreted proteins involved in creating a pro-fibrotic microenvironment include AREG, CTGF, CYR61, FGF1, and MSLN and these YAP1 target genes are highlighted and were chosen for further in vitro confirmation