Search

Abstract: Hepatic progenitor cells (HPCs) persist in adulthood and have the potential to play a major role in regenerating diseased liver. However, the signaling pathways that both directly and indirectly regulate HPCs’ self-renewal and differentiation remain elusive. Previously, we identified a bipotent, stem cell antigen-1 (Sca-1) positive HPC population from naïve adult liver tissue. In the present study, we aimed to investigate the involvement of various signaling pathways in Sca-1+ HPC proliferation. Epidermal growth factor (EGF) supplementation shows a significant increase in Sca-1+ HPC proliferation and colony formation while stimulating phosphorylation of ERK1/2 and activating the induction of Cyclin D1. There were no demonstrable effects of EGF on Akt. The MEK inhibitor, PD0325901, inhibits proliferation and ERK1/2 phosphorylation while also suppressing the expression of Cyclin D1. In addition, activation of either IL-6/STAT3 or Wnt/β-Catenin pathway did not independently support cell proliferation and colony formation of HPCs. The Wnt/β-Catenin pathway can cooperate with EGF to significantly promote HPC colony formation ratio and maintain long-term HPC in vitro. The data indicates that the MAPK/ERK pathway is both essential and critical for HPC proliferation, and the Wnt signaling pathway is not sufficient, while it works synergistically with the MAPK/ERK signaling pathway to promote HPC proliferation. [Copyright &y& Elsevier]

This study aimed to investigate the role for Foxq1 in proliferation activity regulation of dental pulp stem cells (DPSCs). Proliferation of DPSC was induced by calcium hydroxide, then expression alteration of Foxq1 was evaluated. Lentivirus was employed to manipulate Foxq1 level in DPSC, and proliferation activities were evaluated. To look into mechanism regulating Foxq1 level after calcium hydroxide stimulation, expressions of various microRNAs were evaluated, then bioinformatics study and dual-luciferase study were carried out to confirm targeting relationship between microRNA and Foxq1. The result of our study indicated that proliferation activities of DPSCs were enhanced after calcium hydroxide stimulation, during which expression of Foxq1 was also up-regulated. Cell viability and progression from G1 to S phase were both improved with overexpression of Foxq1, and microRNAs profiling study and dual-luciferase result suggested miR-320b contributed to the up-regulation of Foxq1 after calcium hydroxide stimulation. These results suggested that miR-320b mediated Foxq1 up-regulation promote proliferation of dental pulp stem cells. [ABSTRACT FROM AUTHOR]