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Mabuchi, A; Mullaney I; Sheard PW; Hessian PA; Mallard BL; Tawadrous MN; Zimmermann A; Senoo H; Wheatley AM
Journal Of Hepatology
Role of hepatic stellate cell/hepatocyte interaction and activation of hepatic stellate cells in the early phase of liver regeneration in the rat
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Vitamin A-storing cell Desmin α-smooth muscle actin (α-SMA) Partial hepatectomy Intravital fluorescence microscopy
AbstractBackground/AimsHepatic stellate cells (HSCs) are known to play a role in hepatic regeneration. We investigated hepatocyte/HSC interaction and HSC activation at various times after 70% partial hepatectomy (PHx) in the rat.MethodsThe hepatic microcirculation was studied using intravital fluorescence microscopy (IVFM). Desmin and α-SMA within liver tissue were detected by immunohistochemistry. In isolated parenchymal liver cells (PLCs) and HSCs, double immunostaining was used to identify activated HSC.ResultsUsing IVFM, hepatocyte-clusters were often seen in vivo at 3 days after PHx (PHx3). Distance between HSC fell from 61.72.1 μm in controls to 36.11.4 μm (P<0.001) while the HSC/hepatocyte ratio rose (0.710.01 to 1.080.03; P<0.001). In >80% of in vivo microscopic fields in the PHx3 group, clusters of HSCs were observed especially near hepatocyte-clusters. At PHx1 and PHx3, >20% of cells in the PLC-fraction were HSCs which adhered to hepatocytes. At PHx3, in addition to desmin staining, isolated HSCs were also positive for BrdU and α-SMA, and formed clusters. HSCs in the HSC-fraction were only positive for desmin which indicated that adherence to hepatocytes is required for HSC activation.ConclusionsOur data suggest that HSCs are activated by adhering to hepatocytes in the early phase of liver regeneration.
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