IndraLab

"This distribution change may allow outside-in signaling, because the integrin-beta1A+ D extracellular domains may allow interactions between (myo) fibroblasts and/or myocytes and the ECM to " sense " the mechanical wall stress of RV hypertension, septal shift, altered geometry, and increased fibrillar collagen, to trigger RV and septal HP biochemical signaling and ECM remodeling.26, 27 We previously identified the TGF-beta1 pathway as a central mediator of fibrosis in RV pressure load.13 TGF-beta1 binds integrin-beta1, which reciprocally activates latent TGF-beta1 and its profibrotic signaling.28, 29, 30 Consistent with our invitro results, integrin-beta1 inhibition in fibroblasts blocks TGF-beta1 activation and prevents fibrosis.31, 32 Activated TGF-beta1 induces collagen type I production through signaling cascades (eg, Smad2/3), which are active in our models.33, 34, 35, 36 This was supported by our invitro experiments that showed that blocking integrins decreased contractile activity of stretched fibroblasts."