However, Smad2 and Smad3 have a similar structure and are intensely activated in liver fibrosis (Yao et al., 2012), whereas Smad3 directly binds to DNA sequences that regulate a series of fibrogenic (collagen) target genes and markers (α-SMA and E-cadherin), which belongs to Smad3-dependent genes (Latella et al., 2009; Masszi and Kapus, 2011). This evidence concerns the gene ACTA1 and Hepatic fibrosis.