Fig. 2

Mechano-transduction and YAP/TAZ. a Integrin-cytoskeleton-nesprin-SUN-domain protein serves as a mechanical axis passing mechanical force from extracellular matrix to nuclear lamina. Mechano-sensitive integrin mediates extracellular force induced fibrogenic gene (e.g., MCP-1) expression and cytoskeleton reorganization through focal adhesion kinase (FAK)-extracellular regulated protein kinases (ERK) signaling and Rho GTPase, respectively. Intracellular force likewise affects cytoskeletal rearrangement through regulating actin-binding proteins (ABPs), plakin protein family and modification of tubulin (e.g., methylation). Nuclear force regulates chromatin status through interacting with nuclear laminA/C and laminB1/2. b Physical factors in extracellular environment (e.g., shear stress, stiffness, cell geometry) produce mechanical forces. These mechanical forces are transmitted by mechanosensitive transmembrane proteins like TGF-β1 and integrins as well as intracellular proteins, like CCM3, to regulate translocation of YAP/TAZ directly and indirectly. YAP/TAZ is directly phosphorylated by LATS1/2 and retains in cytoplasm to combine with protein 14-3-3 and degrade. Mechanical forces inhibit the phosphorylation of YAP/TAZ to increase the translocation of YAP/TAZ into nucleus, which will induce fibrosis related gene (e.g., IL6, IL8, SELE) expression. Created with BioRender.com. YAP/TAZ Yes-associated protein and transcriptional coactivator with PDZ-binding motif, FAK focal adhesion kinase, ERK extracellular signal-regulated kinase, NPC nuclear pore complex, MCP-1 monocyte chemoattractant protein-1, Tβ4 thymosin β4, Arp2/3 actin-related protein2/3, ECM extracellular matrix, TGF-β1 transforming growth factor-β1, CCM3 cerebral cavernous malformation 3, LATS1/2 large tumor suppressor 1/2, PP1A protein phosphatase 1α, IL interleukin, SELE selectin E, CTGF connective tissue growth factor, PAI-1 plasminogen activator inhibitor-1, LOX lysyl oxidase, TFs transcriptional factors