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A Smad Signaling Network Regulates Islet Cell Proliferation

Pancreatic β-cell loss and dysfunction are critical components of all types of diabetes. Human and rodent β-cells are able to proliferate, and this proliferation is an important defense against the evolution and progression of diabetes. Transforming growth factor-β (TGF-β) signaling has been shown t...

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Autores principales: El-Gohary, Yousef, Tulachan, Sidhartha, Wiersch, John, Guo, Ping, Welsh, Carey, Prasadan, Krishna, Paredes, Jose, Shiota, Chiyo, Xiao, Xiangwei, Wada, Yoko, Diaz, Marilyn, Gittes, George
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868054/
https://www.ncbi.nlm.nih.gov/pubmed/24089514
http://dx.doi.org/10.2337/db13-0432
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author El-Gohary, Yousef
Tulachan, Sidhartha
Wiersch, John
Guo, Ping
Welsh, Carey
Prasadan, Krishna
Paredes, Jose
Shiota, Chiyo
Xiao, Xiangwei
Wada, Yoko
Diaz, Marilyn
Gittes, George
author_facet El-Gohary, Yousef
Tulachan, Sidhartha
Wiersch, John
Guo, Ping
Welsh, Carey
Prasadan, Krishna
Paredes, Jose
Shiota, Chiyo
Xiao, Xiangwei
Wada, Yoko
Diaz, Marilyn
Gittes, George
author_sort El-Gohary, Yousef
collection PubMed
description Pancreatic β-cell loss and dysfunction are critical components of all types of diabetes. Human and rodent β-cells are able to proliferate, and this proliferation is an important defense against the evolution and progression of diabetes. Transforming growth factor-β (TGF-β) signaling has been shown to affect β-cell development, proliferation, and function, but β-cell proliferation is thought to be the only source of new β-cells in the adult. Recently, β-cell dedifferentiation has been shown to be an important contributory mechanism to β-cell failure. In this study, we tie together these two pathways by showing that a network of intracellular TGF-β regulators, smads 7, 2, and 3, control β-cell proliferation after β-cell loss, and specifically, smad7 is necessary for that β-cell proliferation. Importantly, this smad7-mediated proliferation appears to entail passing through a transient, nonpathologic dedifferentiation of β-cells to a pancreatic polypeptide–fold hormone-positive state. TGF-β receptor II appears to be a receptor important for controlling the status of the smad network in β-cells. These studies should help our understanding of properly regulated β-cell replication.
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spelling pubmed-38680542015-01-01 A Smad Signaling Network Regulates Islet Cell Proliferation El-Gohary, Yousef Tulachan, Sidhartha Wiersch, John Guo, Ping Welsh, Carey Prasadan, Krishna Paredes, Jose Shiota, Chiyo Xiao, Xiangwei Wada, Yoko Diaz, Marilyn Gittes, George Diabetes Islet Studies Pancreatic β-cell loss and dysfunction are critical components of all types of diabetes. Human and rodent β-cells are able to proliferate, and this proliferation is an important defense against the evolution and progression of diabetes. Transforming growth factor-β (TGF-β) signaling has been shown to affect β-cell development, proliferation, and function, but β-cell proliferation is thought to be the only source of new β-cells in the adult. Recently, β-cell dedifferentiation has been shown to be an important contributory mechanism to β-cell failure. In this study, we tie together these two pathways by showing that a network of intracellular TGF-β regulators, smads 7, 2, and 3, control β-cell proliferation after β-cell loss, and specifically, smad7 is necessary for that β-cell proliferation. Importantly, this smad7-mediated proliferation appears to entail passing through a transient, nonpathologic dedifferentiation of β-cells to a pancreatic polypeptide–fold hormone-positive state. TGF-β receptor II appears to be a receptor important for controlling the status of the smad network in β-cells. These studies should help our understanding of properly regulated β-cell replication. American Diabetes Association 2014-01 2013-12-13 /pmc/articles/PMC3868054/ /pubmed/24089514 http://dx.doi.org/10.2337/db13-0432 Text en © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Islet Studies
El-Gohary, Yousef
Tulachan, Sidhartha
Wiersch, John
Guo, Ping
Welsh, Carey
Prasadan, Krishna
Paredes, Jose
Shiota, Chiyo
Xiao, Xiangwei
Wada, Yoko
Diaz, Marilyn
Gittes, George
A Smad Signaling Network Regulates Islet Cell Proliferation
title A Smad Signaling Network Regulates Islet Cell Proliferation
title_full A Smad Signaling Network Regulates Islet Cell Proliferation
title_fullStr A Smad Signaling Network Regulates Islet Cell Proliferation
title_full_unstemmed A Smad Signaling Network Regulates Islet Cell Proliferation
title_short A Smad Signaling Network Regulates Islet Cell Proliferation
title_sort smad signaling network regulates islet cell proliferation
topic Islet Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868054/
https://www.ncbi.nlm.nih.gov/pubmed/24089514
http://dx.doi.org/10.2337/db13-0432
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