CCN2(IV) triggers TβRII expression via EGFR/SMAD activation and independently of TGFβ pathway in VSMCs in vitro. The increased expression of TβRII induced by CCN2(IV) after 48 h was significantly reduced in VSMCs preincubated 1 h with SIS3, a pharmacological inhibitor of the SMAD3 activation (A). However, 1 h of preincubation with galunisertib, a pharmacological inhibitor of TβRI, did not prevent TβRII overexpression induced by CCN2(IV) in VSMCs (B). On the other hand, preincubation of VSMCs with erlotinib, a pharmacological inhibitor of EGFR, 1 h before CCN2(IV) addition, significantly prevented TβRII overexpression after 48 h (C). Data are presented as mean ± SEM of 4 independent experiments. * p < 0.05 increased vs. Basal; † p < 0.05 decreased vs. Basal.