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LPS/Bcl3/YAP1 signaling promotes Sox9(+)HNF4α(+) hepatocyte-mediated liver regeneration after hepatectomy

Recent reports have demonstrated that Sox9(+)HNF4α(+) hepatocytes are involved in liver regeneration after chronic liver injury; however, little is known about the origin of Sox9(+)HNF4α(+) hepatocytes and the regulatory mechanism. Employing a combination of chimeric lineage tracing, immunofluoresce...

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Autores principales: Shao, Changchun, Jing, Yingying, Zhao, Shanmin, Yang, Xue, Hu, Yiming, Meng, Yan, Huang, Yihua, Ye, Fei, Gao, Lu, Liu, Wenting, Sheng, Dandan, Li, Rong, Zhang, Xiaoren, Wei, Lixin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964805/
https://www.ncbi.nlm.nih.gov/pubmed/35351855
http://dx.doi.org/10.1038/s41419-022-04715-x
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author Shao, Changchun
Jing, Yingying
Zhao, Shanmin
Yang, Xue
Hu, Yiming
Meng, Yan
Huang, Yihua
Ye, Fei
Gao, Lu
Liu, Wenting
Sheng, Dandan
Li, Rong
Zhang, Xiaoren
Wei, Lixin
author_facet Shao, Changchun
Jing, Yingying
Zhao, Shanmin
Yang, Xue
Hu, Yiming
Meng, Yan
Huang, Yihua
Ye, Fei
Gao, Lu
Liu, Wenting
Sheng, Dandan
Li, Rong
Zhang, Xiaoren
Wei, Lixin
author_sort Shao, Changchun
collection PubMed
description Recent reports have demonstrated that Sox9(+)HNF4α(+) hepatocytes are involved in liver regeneration after chronic liver injury; however, little is known about the origin of Sox9(+)HNF4α(+) hepatocytes and the regulatory mechanism. Employing a combination of chimeric lineage tracing, immunofluorescence, and immunohistochemistry, we demonstrate that Sox9(+)HNF4α(+) hepatocytes, generated by transition from mature hepatocytes, play an important role in the initial phase after partial hepatectomy (PHx). Additionally, knocking down the expression of Sox9 suppresses hepatocyte proliferation and blocks the recovery of lost hepatic tissue. In vitro and in vivo assays demonstrated that Bcl3, activated by LPS, promotes hepatocyte conversion and liver regeneration. Mechanistically, Bcl3 forms a complex with and deubiquitinates YAP1 and further induces YAP1 to translocate into the nucleus, resulting in Sox9 upregulation and mature hepatocyte conversion. We demonstrate that Bcl3 promotes Sox9(+)HNF4α(+) hepatocytes to participate in liver regeneration, and might therefore be a potential target for enhancing regeneration after liver injury.
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spelling pubmed-89648052022-04-12 LPS/Bcl3/YAP1 signaling promotes Sox9(+)HNF4α(+) hepatocyte-mediated liver regeneration after hepatectomy Shao, Changchun Jing, Yingying Zhao, Shanmin Yang, Xue Hu, Yiming Meng, Yan Huang, Yihua Ye, Fei Gao, Lu Liu, Wenting Sheng, Dandan Li, Rong Zhang, Xiaoren Wei, Lixin Cell Death Dis Article Recent reports have demonstrated that Sox9(+)HNF4α(+) hepatocytes are involved in liver regeneration after chronic liver injury; however, little is known about the origin of Sox9(+)HNF4α(+) hepatocytes and the regulatory mechanism. Employing a combination of chimeric lineage tracing, immunofluorescence, and immunohistochemistry, we demonstrate that Sox9(+)HNF4α(+) hepatocytes, generated by transition from mature hepatocytes, play an important role in the initial phase after partial hepatectomy (PHx). Additionally, knocking down the expression of Sox9 suppresses hepatocyte proliferation and blocks the recovery of lost hepatic tissue. In vitro and in vivo assays demonstrated that Bcl3, activated by LPS, promotes hepatocyte conversion and liver regeneration. Mechanistically, Bcl3 forms a complex with and deubiquitinates YAP1 and further induces YAP1 to translocate into the nucleus, resulting in Sox9 upregulation and mature hepatocyte conversion. We demonstrate that Bcl3 promotes Sox9(+)HNF4α(+) hepatocytes to participate in liver regeneration, and might therefore be a potential target for enhancing regeneration after liver injury. Nature Publishing Group UK 2022-03-28 /pmc/articles/PMC8964805/ /pubmed/35351855 http://dx.doi.org/10.1038/s41419-022-04715-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Shao, Changchun
Jing, Yingying
Zhao, Shanmin
Yang, Xue
Hu, Yiming
Meng, Yan
Huang, Yihua
Ye, Fei
Gao, Lu
Liu, Wenting
Sheng, Dandan
Li, Rong
Zhang, Xiaoren
Wei, Lixin
LPS/Bcl3/YAP1 signaling promotes Sox9(+)HNF4α(+) hepatocyte-mediated liver regeneration after hepatectomy
title LPS/Bcl3/YAP1 signaling promotes Sox9(+)HNF4α(+) hepatocyte-mediated liver regeneration after hepatectomy
title_full LPS/Bcl3/YAP1 signaling promotes Sox9(+)HNF4α(+) hepatocyte-mediated liver regeneration after hepatectomy
title_fullStr LPS/Bcl3/YAP1 signaling promotes Sox9(+)HNF4α(+) hepatocyte-mediated liver regeneration after hepatectomy
title_full_unstemmed LPS/Bcl3/YAP1 signaling promotes Sox9(+)HNF4α(+) hepatocyte-mediated liver regeneration after hepatectomy
title_short LPS/Bcl3/YAP1 signaling promotes Sox9(+)HNF4α(+) hepatocyte-mediated liver regeneration after hepatectomy
title_sort lps/bcl3/yap1 signaling promotes sox9(+)hnf4α(+) hepatocyte-mediated liver regeneration after hepatectomy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964805/
https://www.ncbi.nlm.nih.gov/pubmed/35351855
http://dx.doi.org/10.1038/s41419-022-04715-x
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