Estrogen receptors orchestrate cell growth and differentiation to facilitate liver regeneration

Theranostics
Ta-Lun KaoWen-Lung Ma

Abstract

Background and Aims: Improving liver regeneration (LR) capacity and thereby liver function reserve is a critical bridging strategy for managing liver failure patients. Since estrogen signaling may participate in LR, our aim was to characterize the roles of ERα and ERβ in LR. Methods: LR capacity and estradiol levels following 2/3rd partial hepatectomy (PHx) were compared in ERα-KO or ERβ-KO vs. wildtype mice. The ERα- or ERβ-related transcriptome and interactome were analyzed from regenerating livers, and then bioinformatics was used for pathway discovery and analysis of interactome-transcriptome relationships. Human hepatic progenitors (HepRG cells) and mouse Hepa1-6 hepatocytes were used to elucidate molecular interactions and functions. Results: This paper demonstrated that estrogen signals orchestrate hepatic repopulation and differentiation via distinct transcriptome patterns governed by ERα or ERβ. Cell repopulation pathway was associated with the ERα-transcriptome, but cell differentiation and metabolic function were associated with the ERβ transcriptome. Mechanistic studies linking ERs interactomes and transcriptomes discovered that ERα-Chd1 interaction promoted cell growth by upregulating Ssxb6, Crygc, and Cst1; and, E...Continue Reading

Citations

Dec 21, 2019·Journal of Receptor and Signal Transduction Research·Yang YangZhiyun Wang
Jun 1, 2020·Naunyn-Schmiedeberg's Archives of Pharmacology·Mengmeng ZhangJiajia Wang
May 8, 2019·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Alexandra DiliIsabelle A Leclercq
Jun 3, 2020·Cell Death and Differentiation·Sipra MohapatraKohei Ohta
Jun 22, 2020·Differentiation; Research in Biological Diversity·Mathieu DanoyEric Leclerc
Apr 3, 2021·Npj Regenerative Medicine·Julia LosnerJessica L Whited
Aug 16, 2021·Biological Trace Element Research·Ya-Ming YuHong-Wei Wang
Aug 27, 2021·Frontiers in Endocrinology·Chieh-Liang HuangWen-Lung Ma

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Datasets Mentioned

BETA
GTX22746

Methods Mentioned

BETA
transgenic
PCR
in vitro transcription
Feature Extraction
immunoprecipitation
ubiquitination

Software Mentioned

PANTHER
R
Software
Feature Extraction
iProXpress
FIMO
GSEA
MEME
MASCOT

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