A study of Gaudio et al. revealed that this adaptive proliferative response of cholangiocyte to cholestasis is mainly mediated by the upregulation of VEGFR-3 and secretion of VEGF-C, through activation of inositol 1,4,5-triphosphate/[Ca2+]i/protein kinase C alpha and phosphorylation of Src/extracellular signal-regulated kinases 1/2, during the first week after BDL injury [18]. Here, MAPK3 is linked to cholestasis.