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ColXV promotes adipocyte differentiation via inhibiting DNA methylation and cAMP/PKA pathway in mice

Extracellular matrix (ECM), as an essential component of adipose tissue, not only provides mechanical support for adipocyte growth, but also participates in ECM-adipocyte communication via various secreted proteins, including highly enriched collagens. Collagen XV (ColXV) is a secreted non-fibrillar...

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Autores principales: Liu, Guannv, Li, Meihang, Xu, Yatao, Wu, Song, Saeed, Muhammad, Sun, Chao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601127/
https://www.ncbi.nlm.nih.gov/pubmed/28947959
http://dx.doi.org/10.18632/oncotarget.18550
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author Liu, Guannv
Li, Meihang
Xu, Yatao
Wu, Song
Saeed, Muhammad
Sun, Chao
author_facet Liu, Guannv
Li, Meihang
Xu, Yatao
Wu, Song
Saeed, Muhammad
Sun, Chao
author_sort Liu, Guannv
collection PubMed
description Extracellular matrix (ECM), as an essential component of adipose tissue, not only provides mechanical support for adipocyte growth, but also participates in ECM-adipocyte communication via various secreted proteins, including highly enriched collagens. Collagen XV (ColXV) is a secreted non-fibrillar collagen within ECM Basement Membrane (BM) zones and well recognized as a tumor suppressor. However, the role of ColXV in adipose tissue is still unknown. In this study, high fat diet (HFD) fed mice were used as obese model, in which we deeply investigated the interaction between ColXV and adipocyte differentiation or adipose metabolism. We found great elevated ColXV expression and positive effect of ColXV on lipid deposition during adipocyte differentiation or obesity both in vitro and in vivo. cAMP response element binding protein (CREB) is a cellular transcription factor that can inhibit adipogenesis and promote lipolysis. Here we proposed ColXV as a newly discovered downstream gene of CREB. We further proved that CREB can repress adipocyte differentiation and enhance lipolysis by negatively regulating ColXV transcription. Mechanistic studies showed ColXV enhanced adipocyte differentiation and lipid deposition through reducing its DNA methylation and repressing the cAMP/PKA signaling pathway. Collectively, our study identified ColXV as a novel downstream gene for CREB and could promote adipocyte differentiation, inhibit lipolysis through repressing cAMP/PKA signaling pathway and positively regulating adipogenic markers expressions by repressing the activity of maintenance methyltransferase Dnmt1. Our data discovered a novel role of ColXV in adipocyte differentiation and provide insight into obesity and related metabolic diseases.
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spelling pubmed-56011272017-09-25 ColXV promotes adipocyte differentiation via inhibiting DNA methylation and cAMP/PKA pathway in mice Liu, Guannv Li, Meihang Xu, Yatao Wu, Song Saeed, Muhammad Sun, Chao Oncotarget Research Paper Extracellular matrix (ECM), as an essential component of adipose tissue, not only provides mechanical support for adipocyte growth, but also participates in ECM-adipocyte communication via various secreted proteins, including highly enriched collagens. Collagen XV (ColXV) is a secreted non-fibrillar collagen within ECM Basement Membrane (BM) zones and well recognized as a tumor suppressor. However, the role of ColXV in adipose tissue is still unknown. In this study, high fat diet (HFD) fed mice were used as obese model, in which we deeply investigated the interaction between ColXV and adipocyte differentiation or adipose metabolism. We found great elevated ColXV expression and positive effect of ColXV on lipid deposition during adipocyte differentiation or obesity both in vitro and in vivo. cAMP response element binding protein (CREB) is a cellular transcription factor that can inhibit adipogenesis and promote lipolysis. Here we proposed ColXV as a newly discovered downstream gene of CREB. We further proved that CREB can repress adipocyte differentiation and enhance lipolysis by negatively regulating ColXV transcription. Mechanistic studies showed ColXV enhanced adipocyte differentiation and lipid deposition through reducing its DNA methylation and repressing the cAMP/PKA signaling pathway. Collectively, our study identified ColXV as a novel downstream gene for CREB and could promote adipocyte differentiation, inhibit lipolysis through repressing cAMP/PKA signaling pathway and positively regulating adipogenic markers expressions by repressing the activity of maintenance methyltransferase Dnmt1. Our data discovered a novel role of ColXV in adipocyte differentiation and provide insight into obesity and related metabolic diseases. Impact Journals LLC 2017-06-16 /pmc/articles/PMC5601127/ /pubmed/28947959 http://dx.doi.org/10.18632/oncotarget.18550 Text en Copyright: © 2017 Liu et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Liu, Guannv
Li, Meihang
Xu, Yatao
Wu, Song
Saeed, Muhammad
Sun, Chao
ColXV promotes adipocyte differentiation via inhibiting DNA methylation and cAMP/PKA pathway in mice
title ColXV promotes adipocyte differentiation via inhibiting DNA methylation and cAMP/PKA pathway in mice
title_full ColXV promotes adipocyte differentiation via inhibiting DNA methylation and cAMP/PKA pathway in mice
title_fullStr ColXV promotes adipocyte differentiation via inhibiting DNA methylation and cAMP/PKA pathway in mice
title_full_unstemmed ColXV promotes adipocyte differentiation via inhibiting DNA methylation and cAMP/PKA pathway in mice
title_short ColXV promotes adipocyte differentiation via inhibiting DNA methylation and cAMP/PKA pathway in mice
title_sort colxv promotes adipocyte differentiation via inhibiting dna methylation and camp/pka pathway in mice
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601127/
https://www.ncbi.nlm.nih.gov/pubmed/28947959
http://dx.doi.org/10.18632/oncotarget.18550
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