SMAD4 and Hepatic fibrosis: As illustrated in figure seven, B19 NS1 protein aggravates the hepatic fibrosis by enhancing the expression of TGF-β isoforms and activation of Smad2/3, which urge phosphorylated Smad2/3 to cooperate with Smad4 and Sp1 and induce the consequent fiboriss-related proteins, including PAI-1 and α-SMA (Fig 7).