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Cavin1 Deficiency Causes Disorder of Hepatic Glycogen Metabolism and Neonatal Death by Impacting Fenestrations in Liver Sinusoidal Endothelial Cells
It has been reported that Cavin1 deficiency causes lipodystrophy in both humans and mice by affecting lipid metabolism. The ablation of Cavin1 in rodents also causes a significant deviation from Mendelian ratio at weaning in a background‐dependent manner, suggesting the presence of undiscovered func...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539207/ https://www.ncbi.nlm.nih.gov/pubmed/33042738 http://dx.doi.org/10.1002/advs.202000963 |
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author | Wei, Zhuang Lei, Jigang Shen, Feng Dai, Yuxiang Sun, Yan Liu, Yilian Dai, Yan Jian, Zhijie Wang, Shilong Chen, Zhengjun Liao, Kan Hong, Shangyu |
author_facet | Wei, Zhuang Lei, Jigang Shen, Feng Dai, Yuxiang Sun, Yan Liu, Yilian Dai, Yan Jian, Zhijie Wang, Shilong Chen, Zhengjun Liao, Kan Hong, Shangyu |
author_sort | Wei, Zhuang |
collection | PubMed |
description | It has been reported that Cavin1 deficiency causes lipodystrophy in both humans and mice by affecting lipid metabolism. The ablation of Cavin1 in rodents also causes a significant deviation from Mendelian ratio at weaning in a background‐dependent manner, suggesting the presence of undiscovered functions of Cavin1. In the current study, the results show that Cavin1 deficiency causes neonatal death in C57BL/6J mice by dampening the storage and mobilization of glycogen in the liver, which leads to lethal neonatal hypoglycemia. Further investigation by electron microscopy reveals that Cavin1 deficiency impairs the fenestration in liver sinusoidal endothelial cells (LSECs) and impacts the permeability of endothelial barrier in the liver. Mechanistically, Cavin1 deficiency inhibits the RhoA‐Rho‐associated protein kinase 2‐LIM domain kinase‐Cofilin signaling pathway and suppresses the dynamics of the cytoskeleton, and eventually causes the reduction of fenestrae in LSECs. In addition, the defect of fenestration in LSECs caused by Cavin1 deficiency can be rescued by treatment with the F‐actin depolymerization reagent latrunculin A. In summary, the current study reveals a novel function of Cavin1 on fenestrae formation in LSECs and liver glycogen metabolism, which provide an explanation for the neonatal death of Cavin1 null mice and a potential mechanism for metabolic disorders in patients with Cavin1 mutation. |
format | Online Article Text |
id | pubmed-7539207 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75392072020-10-09 Cavin1 Deficiency Causes Disorder of Hepatic Glycogen Metabolism and Neonatal Death by Impacting Fenestrations in Liver Sinusoidal Endothelial Cells Wei, Zhuang Lei, Jigang Shen, Feng Dai, Yuxiang Sun, Yan Liu, Yilian Dai, Yan Jian, Zhijie Wang, Shilong Chen, Zhengjun Liao, Kan Hong, Shangyu Adv Sci (Weinh) Communications It has been reported that Cavin1 deficiency causes lipodystrophy in both humans and mice by affecting lipid metabolism. The ablation of Cavin1 in rodents also causes a significant deviation from Mendelian ratio at weaning in a background‐dependent manner, suggesting the presence of undiscovered functions of Cavin1. In the current study, the results show that Cavin1 deficiency causes neonatal death in C57BL/6J mice by dampening the storage and mobilization of glycogen in the liver, which leads to lethal neonatal hypoglycemia. Further investigation by electron microscopy reveals that Cavin1 deficiency impairs the fenestration in liver sinusoidal endothelial cells (LSECs) and impacts the permeability of endothelial barrier in the liver. Mechanistically, Cavin1 deficiency inhibits the RhoA‐Rho‐associated protein kinase 2‐LIM domain kinase‐Cofilin signaling pathway and suppresses the dynamics of the cytoskeleton, and eventually causes the reduction of fenestrae in LSECs. In addition, the defect of fenestration in LSECs caused by Cavin1 deficiency can be rescued by treatment with the F‐actin depolymerization reagent latrunculin A. In summary, the current study reveals a novel function of Cavin1 on fenestrae formation in LSECs and liver glycogen metabolism, which provide an explanation for the neonatal death of Cavin1 null mice and a potential mechanism for metabolic disorders in patients with Cavin1 mutation. John Wiley and Sons Inc. 2020-08-21 /pmc/articles/PMC7539207/ /pubmed/33042738 http://dx.doi.org/10.1002/advs.202000963 Text en © 2020 The Authors. Published by Wiley‐VCH GmbH This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Communications Wei, Zhuang Lei, Jigang Shen, Feng Dai, Yuxiang Sun, Yan Liu, Yilian Dai, Yan Jian, Zhijie Wang, Shilong Chen, Zhengjun Liao, Kan Hong, Shangyu Cavin1 Deficiency Causes Disorder of Hepatic Glycogen Metabolism and Neonatal Death by Impacting Fenestrations in Liver Sinusoidal Endothelial Cells |
title | Cavin1 Deficiency Causes Disorder of Hepatic Glycogen Metabolism and Neonatal Death by Impacting Fenestrations in Liver Sinusoidal Endothelial Cells |
title_full | Cavin1 Deficiency Causes Disorder of Hepatic Glycogen Metabolism and Neonatal Death by Impacting Fenestrations in Liver Sinusoidal Endothelial Cells |
title_fullStr | Cavin1 Deficiency Causes Disorder of Hepatic Glycogen Metabolism and Neonatal Death by Impacting Fenestrations in Liver Sinusoidal Endothelial Cells |
title_full_unstemmed | Cavin1 Deficiency Causes Disorder of Hepatic Glycogen Metabolism and Neonatal Death by Impacting Fenestrations in Liver Sinusoidal Endothelial Cells |
title_short | Cavin1 Deficiency Causes Disorder of Hepatic Glycogen Metabolism and Neonatal Death by Impacting Fenestrations in Liver Sinusoidal Endothelial Cells |
title_sort | cavin1 deficiency causes disorder of hepatic glycogen metabolism and neonatal death by impacting fenestrations in liver sinusoidal endothelial cells |
topic | Communications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539207/ https://www.ncbi.nlm.nih.gov/pubmed/33042738 http://dx.doi.org/10.1002/advs.202000963 |
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