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Adipocyte Fatty Acid Binding Protein Promotes the Onset and Progression of Liver Fibrosis via Mediating the Crosstalk between Liver Sinusoidal Endothelial Cells and Hepatic Stellate Cells
Development of liver fibrosis results in drastic changes in the liver microenvironment, which in turn accelerates disease progression. Although the pathological function of various hepatic cells in fibrogenesis is identified, the crosstalk between them remains obscure. The present study demonstrates...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188197/ https://www.ncbi.nlm.nih.gov/pubmed/34105268 http://dx.doi.org/10.1002/advs.202003721 |
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author | Wu, Xiaoping Shu, Lingling Zhang, Zixuan Li, Jingjing Zong, Jiuyu Cheong, Lai Yee Ye, Dewei Lam, Karen S. L. Song, Erfei Wang, Cunchuan Xu, Aimin Hoo, Ruby L. C. |
author_facet | Wu, Xiaoping Shu, Lingling Zhang, Zixuan Li, Jingjing Zong, Jiuyu Cheong, Lai Yee Ye, Dewei Lam, Karen S. L. Song, Erfei Wang, Cunchuan Xu, Aimin Hoo, Ruby L. C. |
author_sort | Wu, Xiaoping |
collection | PubMed |
description | Development of liver fibrosis results in drastic changes in the liver microenvironment, which in turn accelerates disease progression. Although the pathological function of various hepatic cells in fibrogenesis is identified, the crosstalk between them remains obscure. The present study demonstrates that hepatic expression of adipocyte fatty acid binding protein (A‐FABP) is induced especially in the liver sinusoidal endothelial cells (LSECs) in mice after bile duct ligation (BDL). Genetic ablation and pharmacological inhibition of A‐FABP attenuate BDL‐ or carbon tetrachloride‐induced liver fibrosis in mice associating with reduced collagen accumulation, LSEC capillarization, and hepatic stellate cell (HSC) activation. Mechanistically, elevated A‐FABP promotes LSEC capillarization by activating Hedgehog signaling, thus impairs the gatekeeper function of LSEC on HSC activation. LSEC‐derived A‐FABP also acts on HSCs in paracrine manner to potentiate the transactivation of transforming growth factor β1 (TGFβ1) by activating c‐Jun N‐terminal kinase (JNK)/c‐Jun signaling. Elevated TGFβ1 subsequently exaggerates liver fibrosis. These findings uncover a novel pathological mechanism of liver fibrosis in which LSEC‐derived A‐FABP is a key regulator modulating the onset and progression of the disease. Targeting A‐FABP may represent a potential approach against liver fibrosis. |
format | Online Article Text |
id | pubmed-8188197 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81881972021-06-16 Adipocyte Fatty Acid Binding Protein Promotes the Onset and Progression of Liver Fibrosis via Mediating the Crosstalk between Liver Sinusoidal Endothelial Cells and Hepatic Stellate Cells Wu, Xiaoping Shu, Lingling Zhang, Zixuan Li, Jingjing Zong, Jiuyu Cheong, Lai Yee Ye, Dewei Lam, Karen S. L. Song, Erfei Wang, Cunchuan Xu, Aimin Hoo, Ruby L. C. Adv Sci (Weinh) Full Papers Development of liver fibrosis results in drastic changes in the liver microenvironment, which in turn accelerates disease progression. Although the pathological function of various hepatic cells in fibrogenesis is identified, the crosstalk between them remains obscure. The present study demonstrates that hepatic expression of adipocyte fatty acid binding protein (A‐FABP) is induced especially in the liver sinusoidal endothelial cells (LSECs) in mice after bile duct ligation (BDL). Genetic ablation and pharmacological inhibition of A‐FABP attenuate BDL‐ or carbon tetrachloride‐induced liver fibrosis in mice associating with reduced collagen accumulation, LSEC capillarization, and hepatic stellate cell (HSC) activation. Mechanistically, elevated A‐FABP promotes LSEC capillarization by activating Hedgehog signaling, thus impairs the gatekeeper function of LSEC on HSC activation. LSEC‐derived A‐FABP also acts on HSCs in paracrine manner to potentiate the transactivation of transforming growth factor β1 (TGFβ1) by activating c‐Jun N‐terminal kinase (JNK)/c‐Jun signaling. Elevated TGFβ1 subsequently exaggerates liver fibrosis. These findings uncover a novel pathological mechanism of liver fibrosis in which LSEC‐derived A‐FABP is a key regulator modulating the onset and progression of the disease. Targeting A‐FABP may represent a potential approach against liver fibrosis. John Wiley and Sons Inc. 2021-03-27 /pmc/articles/PMC8188197/ /pubmed/34105268 http://dx.doi.org/10.1002/advs.202003721 Text en © 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Full Papers Wu, Xiaoping Shu, Lingling Zhang, Zixuan Li, Jingjing Zong, Jiuyu Cheong, Lai Yee Ye, Dewei Lam, Karen S. L. Song, Erfei Wang, Cunchuan Xu, Aimin Hoo, Ruby L. C. Adipocyte Fatty Acid Binding Protein Promotes the Onset and Progression of Liver Fibrosis via Mediating the Crosstalk between Liver Sinusoidal Endothelial Cells and Hepatic Stellate Cells |
title | Adipocyte Fatty Acid Binding Protein Promotes the Onset and Progression of Liver Fibrosis via Mediating the Crosstalk between Liver Sinusoidal Endothelial Cells and Hepatic Stellate Cells |
title_full | Adipocyte Fatty Acid Binding Protein Promotes the Onset and Progression of Liver Fibrosis via Mediating the Crosstalk between Liver Sinusoidal Endothelial Cells and Hepatic Stellate Cells |
title_fullStr | Adipocyte Fatty Acid Binding Protein Promotes the Onset and Progression of Liver Fibrosis via Mediating the Crosstalk between Liver Sinusoidal Endothelial Cells and Hepatic Stellate Cells |
title_full_unstemmed | Adipocyte Fatty Acid Binding Protein Promotes the Onset and Progression of Liver Fibrosis via Mediating the Crosstalk between Liver Sinusoidal Endothelial Cells and Hepatic Stellate Cells |
title_short | Adipocyte Fatty Acid Binding Protein Promotes the Onset and Progression of Liver Fibrosis via Mediating the Crosstalk between Liver Sinusoidal Endothelial Cells and Hepatic Stellate Cells |
title_sort | adipocyte fatty acid binding protein promotes the onset and progression of liver fibrosis via mediating the crosstalk between liver sinusoidal endothelial cells and hepatic stellate cells |
topic | Full Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188197/ https://www.ncbi.nlm.nih.gov/pubmed/34105268 http://dx.doi.org/10.1002/advs.202003721 |
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