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Title: MAPK/ERK and Wnt/{beta}-Catenin pathways are synergistically involved in proliferation of Sca-1 positive hepatic progenitor cells

Abstract

Highlights: {yields} Activation of MAPK/ERK pathway with epidermal growth factor (EGF) significantly increased Sca-1{sup +} HPC proliferation and colony formation. {yields} Activation of either IL-6/STAT3 or Wnt/{beta}-Catenin pathway did not independently support cell proliferation and colony formation of HPCs. {yields} Wnt/{beta}-Catenin pathway can cooperate with EGF to significantly promote HPC colony formation and maintain long-term HPCs in vitro. -- 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 naive adult liver tissue. In the present study, we aimed to investigate the involvement of various signaling pathways in Sca-1{sup +} HPC proliferation. Epidermal growth factor (EGF) supplementation shows a significant increase in Sca-1{sup +} 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/{beta}-Catenin pathway did not independently supportmore » cell proliferation and colony formation of HPCs. The Wnt/{beta}-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.« less

Authors:
 [1]; ; ;  [1]
  1. Department of Surgery, University of North Carolina at Chapel Hill (United States)
Publication Date:
OSTI Identifier:
22204957
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 409; Journal Issue: 4; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; ANTIGENS; BIOLOGICAL FUNCTIONS; CELL PROLIFERATION; COLONY FORMATION; DISEASES; GENE REGULATION; GROWTH FACTORS; IN VITRO; LIVER; PHOSPHORYLATION; STEM CELLS

Citation Formats

Jin, Caixia, Department of Medical Genetics and Cell Biology, Ningxia Medical University, Yinchuan 750004, Samuelson, Lisa, Cui, Cai-Bin, Sun, Yangzhong, Gerber, David A., E-mail: david_gerber@med.unc.edu, and Lineberger Cancer Center, University of North Carolina at Chapel Hill. MAPK/ERK and Wnt/{beta}-Catenin pathways are synergistically involved in proliferation of Sca-1 positive hepatic progenitor cells. United States: N. p., 2011. Web. doi:10.1016/J.BBRC.2011.05.094.
Jin, Caixia, Department of Medical Genetics and Cell Biology, Ningxia Medical University, Yinchuan 750004, Samuelson, Lisa, Cui, Cai-Bin, Sun, Yangzhong, Gerber, David A., E-mail: david_gerber@med.unc.edu, & Lineberger Cancer Center, University of North Carolina at Chapel Hill. MAPK/ERK and Wnt/{beta}-Catenin pathways are synergistically involved in proliferation of Sca-1 positive hepatic progenitor cells. United States. https://doi.org/10.1016/J.BBRC.2011.05.094
Jin, Caixia, Department of Medical Genetics and Cell Biology, Ningxia Medical University, Yinchuan 750004, Samuelson, Lisa, Cui, Cai-Bin, Sun, Yangzhong, Gerber, David A., E-mail: david_gerber@med.unc.edu, and Lineberger Cancer Center, University of North Carolina at Chapel Hill. 2011. "MAPK/ERK and Wnt/{beta}-Catenin pathways are synergistically involved in proliferation of Sca-1 positive hepatic progenitor cells". United States. https://doi.org/10.1016/J.BBRC.2011.05.094.
@article{osti_22204957,
title = {MAPK/ERK and Wnt/{beta}-Catenin pathways are synergistically involved in proliferation of Sca-1 positive hepatic progenitor cells},
author = {Jin, Caixia and Department of Medical Genetics and Cell Biology, Ningxia Medical University, Yinchuan 750004 and Samuelson, Lisa and Cui, Cai-Bin and Sun, Yangzhong and Gerber, David A., E-mail: david_gerber@med.unc.edu and Lineberger Cancer Center, University of North Carolina at Chapel Hill},
abstractNote = {Highlights: {yields} Activation of MAPK/ERK pathway with epidermal growth factor (EGF) significantly increased Sca-1{sup +} HPC proliferation and colony formation. {yields} Activation of either IL-6/STAT3 or Wnt/{beta}-Catenin pathway did not independently support cell proliferation and colony formation of HPCs. {yields} Wnt/{beta}-Catenin pathway can cooperate with EGF to significantly promote HPC colony formation and maintain long-term HPCs in vitro. -- 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 naive adult liver tissue. In the present study, we aimed to investigate the involvement of various signaling pathways in Sca-1{sup +} HPC proliferation. Epidermal growth factor (EGF) supplementation shows a significant increase in Sca-1{sup +} 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/{beta}-Catenin pathway did not independently support cell proliferation and colony formation of HPCs. The Wnt/{beta}-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.},
doi = {10.1016/J.BBRC.2011.05.094},
url = {https://www.osti.gov/biblio/22204957}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 409,
place = {United States},
year = {Fri Jun 17 00:00:00 EDT 2011},
month = {Fri Jun 17 00:00:00 EDT 2011}
}