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Maternal embryonic leucine zipper kinase regulates pancreatic ductal, but not β‐cell, regeneration

The maternal embryonic leucine zipper kinase (MELK) is expressed in stem/progenitor cells in some adult tissues, where it has been implicated in diverse biological processes, including the control of cell proliferation. Here, we described studies on its role in adult pancreatic regeneration in respo...

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Autores principales: Chung, Cheng‐Ho, Miller, Amber, Panopoulos, Andreas, Hao, Ergeng, Margolis, Robert, Terskikh, Alexey, Levine, Fred
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wiley Periodicals, Inc. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270240/
https://www.ncbi.nlm.nih.gov/pubmed/25194022
http://dx.doi.org/10.14814/phy2.12131
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author Chung, Cheng‐Ho
Miller, Amber
Panopoulos, Andreas
Hao, Ergeng
Margolis, Robert
Terskikh, Alexey
Levine, Fred
author_facet Chung, Cheng‐Ho
Miller, Amber
Panopoulos, Andreas
Hao, Ergeng
Margolis, Robert
Terskikh, Alexey
Levine, Fred
author_sort Chung, Cheng‐Ho
collection PubMed
description The maternal embryonic leucine zipper kinase (MELK) is expressed in stem/progenitor cells in some adult tissues, where it has been implicated in diverse biological processes, including the control of cell proliferation. Here, we described studies on its role in adult pancreatic regeneration in response to injury induced by duct ligation and β‐cell ablation. MELK expression was studied using transgenic mice expressing GFP under the control of the MELK promoter, and the role of MELK was studied using transgenic mice deleted in the MELK kinase domain. Pancreatic damage was initiated using duct ligation and chemical beta‐cell ablation. By tracing MELK expression using a MELK promoter‐GFP transgene, we determined that expression was extremely low in the normal pancreas. However, following duct ligation and β‐cell ablation, it became highly expressed in pancreatic ductal cells while remaining weakly expressed in α‐cells and β‐ cells. In a mutant mouse in which the MELK kinase domain was deleted, there was no effect on pancreatic development. There was no apparent effect on islet regeneration, either. However, following duct ligation there was a dramatic increase in the number of small ducts, but no change in the total number of duct cells or duct cell proliferation. In vitro studies indicated that this was likely due to a defect in cell migration. These results implicate MELK in the control of the response of the pancreas to injury, specifically controlling cell migration in normal and transformed pancreatic duct cells.
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spelling pubmed-42702402014-12-24 Maternal embryonic leucine zipper kinase regulates pancreatic ductal, but not β‐cell, regeneration Chung, Cheng‐Ho Miller, Amber Panopoulos, Andreas Hao, Ergeng Margolis, Robert Terskikh, Alexey Levine, Fred Physiol Rep Original Research The maternal embryonic leucine zipper kinase (MELK) is expressed in stem/progenitor cells in some adult tissues, where it has been implicated in diverse biological processes, including the control of cell proliferation. Here, we described studies on its role in adult pancreatic regeneration in response to injury induced by duct ligation and β‐cell ablation. MELK expression was studied using transgenic mice expressing GFP under the control of the MELK promoter, and the role of MELK was studied using transgenic mice deleted in the MELK kinase domain. Pancreatic damage was initiated using duct ligation and chemical beta‐cell ablation. By tracing MELK expression using a MELK promoter‐GFP transgene, we determined that expression was extremely low in the normal pancreas. However, following duct ligation and β‐cell ablation, it became highly expressed in pancreatic ductal cells while remaining weakly expressed in α‐cells and β‐ cells. In a mutant mouse in which the MELK kinase domain was deleted, there was no effect on pancreatic development. There was no apparent effect on islet regeneration, either. However, following duct ligation there was a dramatic increase in the number of small ducts, but no change in the total number of duct cells or duct cell proliferation. In vitro studies indicated that this was likely due to a defect in cell migration. These results implicate MELK in the control of the response of the pancreas to injury, specifically controlling cell migration in normal and transformed pancreatic duct cells. Wiley Periodicals, Inc. 2014-09-04 /pmc/articles/PMC4270240/ /pubmed/25194022 http://dx.doi.org/10.14814/phy2.12131 Text en © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Chung, Cheng‐Ho
Miller, Amber
Panopoulos, Andreas
Hao, Ergeng
Margolis, Robert
Terskikh, Alexey
Levine, Fred
Maternal embryonic leucine zipper kinase regulates pancreatic ductal, but not β‐cell, regeneration
title Maternal embryonic leucine zipper kinase regulates pancreatic ductal, but not β‐cell, regeneration
title_full Maternal embryonic leucine zipper kinase regulates pancreatic ductal, but not β‐cell, regeneration
title_fullStr Maternal embryonic leucine zipper kinase regulates pancreatic ductal, but not β‐cell, regeneration
title_full_unstemmed Maternal embryonic leucine zipper kinase regulates pancreatic ductal, but not β‐cell, regeneration
title_short Maternal embryonic leucine zipper kinase regulates pancreatic ductal, but not β‐cell, regeneration
title_sort maternal embryonic leucine zipper kinase regulates pancreatic ductal, but not β‐cell, regeneration
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270240/
https://www.ncbi.nlm.nih.gov/pubmed/25194022
http://dx.doi.org/10.14814/phy2.12131
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