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Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster

The imbalance between transforming growth factor β and bone morphogenetic protein 7 signaling pathways is a critical step in promoting hepatic stellate cell activation during hepatic fibrogenesis. Gremlin1 may impair the balance. Something remains unclear about the regulatory mechanisms of gremlin1...

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Autores principales: Zeng, Xian-Yi, Zhang, Yan-Qiong, He, Xiao-Min, Wan, Lin-Yan, Wang, Hu, Ni, Yi-Ran, Wang, Jie, Wu, Jiang-Feng, Liu, Chang-Bai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349907/
https://www.ncbi.nlm.nih.gov/pubmed/27863390
http://dx.doi.org/10.18632/oncotarget.13365
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author Zeng, Xian-Yi
Zhang, Yan-Qiong
He, Xiao-Min
Wan, Lin-Yan
Wang, Hu
Ni, Yi-Ran
Wang, Jie
Wu, Jiang-Feng
Liu, Chang-Bai
author_facet Zeng, Xian-Yi
Zhang, Yan-Qiong
He, Xiao-Min
Wan, Lin-Yan
Wang, Hu
Ni, Yi-Ran
Wang, Jie
Wu, Jiang-Feng
Liu, Chang-Bai
author_sort Zeng, Xian-Yi
collection PubMed
description The imbalance between transforming growth factor β and bone morphogenetic protein 7 signaling pathways is a critical step in promoting hepatic stellate cell activation during hepatic fibrogenesis. Gremlin1 may impair the balance. Something remains unclear about the regulatory mechanisms of gremlin1 action on hepatic stellate cell activation and hepatic fibrosis. In the current study, gremlin1 overexpression promotes activation of hepatic stellate cells. Knockdown of gremlin1 with siRNAs suppresses hepatic stellate cell activation and attenuates hepatic fibrosis in rat model. Our results also show that miR-23b/27b cluster members bind to 3′-untranslated region of gremlin1 resulting in reduction of transforming growth factor β, α-smooth muscle actin and collagenI α1/2 gene expression. Our findings suggest that gremlin1 promotes hepatic stellate cell activation and hepatic fibrogenesis through impairment of the balance between transforming growth factor β and bone morphogenetic protein 7 signaling pathways. The miR-23b/27b cluster suppresses activation of hepatic stellate cells through binding gremlin1 to rectify the imbalance.
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spelling pubmed-53499072017-04-06 Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster Zeng, Xian-Yi Zhang, Yan-Qiong He, Xiao-Min Wan, Lin-Yan Wang, Hu Ni, Yi-Ran Wang, Jie Wu, Jiang-Feng Liu, Chang-Bai Oncotarget Research Paper The imbalance between transforming growth factor β and bone morphogenetic protein 7 signaling pathways is a critical step in promoting hepatic stellate cell activation during hepatic fibrogenesis. Gremlin1 may impair the balance. Something remains unclear about the regulatory mechanisms of gremlin1 action on hepatic stellate cell activation and hepatic fibrosis. In the current study, gremlin1 overexpression promotes activation of hepatic stellate cells. Knockdown of gremlin1 with siRNAs suppresses hepatic stellate cell activation and attenuates hepatic fibrosis in rat model. Our results also show that miR-23b/27b cluster members bind to 3′-untranslated region of gremlin1 resulting in reduction of transforming growth factor β, α-smooth muscle actin and collagenI α1/2 gene expression. Our findings suggest that gremlin1 promotes hepatic stellate cell activation and hepatic fibrogenesis through impairment of the balance between transforming growth factor β and bone morphogenetic protein 7 signaling pathways. The miR-23b/27b cluster suppresses activation of hepatic stellate cells through binding gremlin1 to rectify the imbalance. Impact Journals LLC 2016-11-15 /pmc/articles/PMC5349907/ /pubmed/27863390 http://dx.doi.org/10.18632/oncotarget.13365 Text en Copyright: © 2016 Zeng et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zeng, Xian-Yi
Zhang, Yan-Qiong
He, Xiao-Min
Wan, Lin-Yan
Wang, Hu
Ni, Yi-Ran
Wang, Jie
Wu, Jiang-Feng
Liu, Chang-Bai
Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster
title Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster
title_full Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster
title_fullStr Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster
title_full_unstemmed Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster
title_short Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster
title_sort suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the mir-23b/27b cluster
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349907/
https://www.ncbi.nlm.nih.gov/pubmed/27863390
http://dx.doi.org/10.18632/oncotarget.13365
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