Expectedly, our data suggested that miR-21 could contribute to the accumulation of fibroblasts not only by stimulating HSC activation via inhibiting SPRY2 expression to increase ERK1 signaling, but also by triggering EMT of hepatocytes via downregulating HNF4α. In view of previous studies and our present work, miR-21 is integrally involved in multiple pathways and profibrotic network in fibroblast transformation of quiescent HSCs and hepatocytes, including TGFβ1/smad, NF-κB, ERK1 signaling and EMT, suggesting that miR-21 may serve as a ‘super’ regulatory miRNA in liver fibrosis. The gene discussed is MAPK3; the disease is Hepatic fibrosis.