Small hepatocyte-like progenitor cells may be a Hedgehog signaling pathway-controlled subgroup of liver stem cells

The present study aimed to investigate the expression levels of components of the Hedgehog signaling pathway (HH) during the proliferation of a liver stem cell subgroup, namely small hepatocyte-like progenitor cells (SHPCs). Retrorsine-treated Fisher 344 rats underwent a partial hepatectomy (PH) to induce the proliferation of SHPCs, after which reverse transcription-polymerase chain reaction (PCR), quantitative PCR, immunohistochemistry and western blot analysis were performed to analyze the expression of various components of the HH in primary SHPCs at different times points post-PH. A number of components of the HH, including Indian hedgehog (IHH), patched (PTCH), smoothened and glioma-associated oncogene (GLI)1, 2 and 3, were continuously expressed and showed dynamic changes in proliferating SHPCs. In addition, the expression levels of IHH, PTCH and GLI1 were significantly different as compared with those of the control group at the same time point, and there were significant differences among the various time points in the experimental group (P<0.01). Furthermore, there was an association between the postoperative day and expression levels of HH components in the retrorsine-treated group. An immunohistochemical analysis demonstrated that PTCH was also expressed at the protein level. In conclusion, the results of the present study suggested that the HH was continuously activated during the proliferation of SHPCs, thus indicating that SHPCs may be a subgroup of stem cells that are regulated by the HH.