SMAD4 and Schnyder corneal dystrophy: Additionally, SMAD3 down-regulation has been documented in models of kidney fibrosis and may play a role in fine-tuning TGFβ signals.33 We confirmed that VPA-mediated inhibition of TGFβ1 signalling was marked by suppression of SMAD4 and identified changes in the TGFβ1 reporter gene, TGFβ1|1, which was linked to the extent of fibrosis in SCD patients.