Effect of the transdifferentiation of BECs into myofibroblasts on the pathogenesis of secondary cholestatic hepatic fibrosis.

The present study investigated the effect of the transdifferentiation of bile duct epithelial cells (BECs) into myofibroblasts on the pathogenesis of secondary cholestatic hepatic fibrosis and examined the underlying mechanisms. A total of 60 male rats with hepatic fibrosis were randomly divided into two groups: A secondary cholestatic hepatic fibrosis model group induced by ligation of the bile duct (BDL) and a sham group, which only underwent segregation of the choledochus. Rats in the BDL group were dynamically observed after week 1, 2, 3 and 4 post-BDL, and the remaining rats were sacrificed after week 5 to determine histological changes and hydroxyproline content. The cellular co-localization of cytokeratin (CK)7/-smooth muscle actin (SMA) or -SMA/desmin was detected by immunofluorescence staining and laser confocal microscopy, while the protein expression levels of CK7, -SMA and desmin were determined by western blot analysis. Sirius red staining was also performed and quantified. The results revealed a significant correlation between the protein expression of CK7 and -SMA (r=0.9692, P<0.01). Furthermore, a predominant correlation between the number of cells stained for CK7/-SMA and collagen deposition in liver tissues was identified, while the correlation of cells with co-localized -SMA and desmin was less pronounced. The transdifferentiation of BECs into myofibroblasts may be a key pathological factor in secondary cholestatic hepatic fibrosis formation.