Tanizaki Yuta, Wang Shouhong, Zhang Hongen, Shibata Yuki, Shi Yun-Bo
Section on Molecular Morphogenesis, Cell Regulation and Development Affinity Group and Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA.
Bioinformatics and Scientific Programming Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA.
iScience. 2023 Feb 28;26(4):106301. doi: 10.1016/j.isci.2023.106301. eCollection 2023 Apr 21.
Thyroid hormone (T3) regulates vertebrate organ development, growth, and metabolism through the T3 receptor (TR). Due to maternal influence in mammals, it has been difficult to study if and how T3 regulates liver development. Liver remodeling during anuran metamorphosis resembles liver maturation in mammals and is controlled by T3. We generated Xenopus tropicalis animals with both TRα and TRβ genes knocked out and found that TR double knockout liver had developmental defects such as reduced cell proliferation and failure to undergo hepatocyte hypertrophy or activate urea cycle gene expression. RNA-seq analysis showed that T3 activated canonical Wnt pathway in the liver. Particularly, Wnt11 was activated in both fibroblasts and hepatic cells, and in turn, likely promoted the proliferation and maturation of hepatocytes. Our study offers new insights into not only how T3 regulates liver development but also on potential means to improve liver regeneration.
甲状腺激素（T3）通过T3受体（TR）调节脊椎动物的器官发育、生长和代谢。由于哺乳动物存在母体影响，因此很难研究T3是否以及如何调节肝脏发育。无尾类动物变态发育期间的肝脏重塑类似于哺乳动物的肝脏成熟，且受T3控制。我们构建了TRα和TRβ基因均敲除的热带爪蟾动物模型，发现TR双敲除肝脏存在发育缺陷，如细胞增殖减少、无法发生肝细胞肥大或激活尿素循环基因表达。RNA测序分析表明，T3在肝脏中激活了经典Wnt信号通路。特别是，Wnt11在成纤维细胞和肝细胞中均被激活，进而可能促进肝细胞的增殖和成熟。我们的研究不仅为T3如何调节肝脏发育提供了新见解，也为改善肝脏再生的潜在方法提供了新见解。
