Figure 6.

Model of adrenomedullin-induced regulation of rheumatoid fibroblast-like synoviocyte (RA-FLS) adhesion by the CLR-RAMP/PKA pathway. Adrenomedullin (AM) activates RA-FLS adhesion to the extracellular matrix proteins vitronectin, fibronectin, and type I collagen. The AM-receptor antagonist (22-52)AM and silencing of RAMP-2 inhibited AM-induced RA-FLS adhesion of CLR/RAMP results in activation of PKA, as assessed by its inhibition by H-89. AM triggers a talin-β₁ chain interaction, disrupting the salt bridge between the α and β subunits and thereby activating the integrins, explaining the increase in RA-FLS adhesion.