During the ductal plate remodeling stage, these α-SMA–positive cells disappear, and cells expressing vimentin, believed to be PFs, begin
to appear24; it appears likely that both PFs and vascular smooth muscle cells are derived from the early α-SMA–positive mesenchymal cells. Immunostaining data suggest that portal myofibroblasts are important mediators of biliary development (potentially through production of extracellular matrix components such as laminin and collagen IV) and that they also contribute to hepatic arterial development.25 A recent study showed that p75 neurotrophin receptor (p75NTR)-expressing mesenchymal cells in the mouse fetal liver include precursors for both HSCs and PFs. p75NTR-positive cells were initially localized to the periphery of the liver bud but then divided Metformin cell line into distinct parenchymal and portal populations, presumably Akt inhibitor reflecting HSCs and PFs. Because the portal population of p75NTR-positive cells expressed the Notch ligand Jagged1, these cells may regulate the commitment of hepatoblasts to a biliary lineage.26 Lineage tracing analyses using mouse embryos expressing a LacZ reporter gene under
the control of the mesodermal marker MesP1 demonstrated a mesodermal origin for HSCs and perivascular mesenchymal cells (desmin+, p75NTR+, α-SMA+) as well as a population of submesothelial cells.27 The perivascular mesenchymal cells described may be PF precursors. Interestingly, this would suggest that HSCs and PFs originate from a common precursor in the early embryo. PFs in the normal liver are similar to other fibroblasts, and elastin-expressing PFs in culture can be stained with the marker TE-7, considered to be definitive for fibroblasts (Fig. 2).28 PFs, like most fibroblasts, are characterized by two key features: prominent endoplasmic reticulum, especially rough endoplasmic reticulum, and elongated and thin cytoplasmic processes.1 Their Golgi complexes are relatively small.29 PFs have dendrite-like cell
extensions that extend to within submicron distances click here of the basolateral membranes of BDE; these extensions have been reported to increase in number in response to injury.30 PFs undergo myofibroblastic differentiation in the chronically injured liver and when cultured on plastic or glass. Portal myofibroblasts, like typical myofibroblasts, express large numbers of α-SMA–containing microfilament bundles arrayed in parallel to the long axis of the cell. In the livers of alcohol-fed but not normal baboons, portal myofibroblasts express pinocytic vesicles.31 Rough endoplasmic reticulum and Golgi complexes are more prominent in myofibroblastic PFs than in normal PFs.29 Relative to HSC-derived myofibroblasts, portal myofibroblasts demonstrate more variability in size.