PAR3介导肝细胞增殖、成熟和结构在肝脏发育和再生中的协调
PAR3-mediated coordination of hepatocyte proliferation, maturation, and architecture in liver development and regeneration.
摘要(中文译文)
肝脏协调细胞增殖、极化与成熟并使之与结构组装相匹配的能力，是其代谢功能和再生能力的基础。然而，整合这些过程的机制仍未被完全阐明。利用小鼠和人类模型，我们发现肝脏极性和毛细胆管（bile canaliculi，BC）的形成在肝母细胞阶段的细胞分裂位点起始，并且BC的延伸在时间上与肝细胞分化过程中的定向细胞分裂相关联。该过程涉及PAR3和YAP依赖性的ERK/MAPK信号调控。PAR3形成蛋白复合物，将一部分IQGAP1定位至紧密连接，从而限制基底外侧膜的ERK/MAPK激活。这种调控是高效BC延伸和肝细胞成熟所必需的。总之，这些发现揭示了一种依赖阶段的机制，将肝脏结构与功能成熟联系起来，并为肝脏发育、再生以及代谢性肝病和肝衰竭的潜在治疗策略提供了见解。
Abstract
The liver's ability to coordinate cell proliferation, polarization, and maturation with architectural assembly is fundamental to its metabolic functions and regenerative capacity. However, the mechanisms that integrate these processes remain incompletely understood. Using murine and human models, we show that hepatic polarity and bile canaliculi (BC) formation initiate at sites of cell division during the hepatoblast stage, and that BC elongation is temporally associated with oriented cell division during hepatocyte differentiation. This process involves PAR3- and YAP-dependent modulation of ERK/MAPK signaling. PAR3 forms a protein complex that localizes a subset of IQGAP1 to tight junctions, thereby restricting ERK/MAPK activation at the basolateral membrane. This regulation is required for efficient BC elongation and hepatocyte maturation. Together, these findings reveal a stage-dependent mechanism linking liver architecture to functional maturation and provide insights into liver development, regeneration, and potential therapeutic strategies for metabolic liver disease and liver failure.
如何引用
AMA
Li Yang, Yu-Heng Zhou, Junya Hayase, Lei Wang, Weiguang Zhang, Erfei Bi, et al. PAR3-mediated coordination of hepatocyte proliferation, maturation, and architecture in liver development and regeneration.. Nature communications. 2026; doi:10.1038/s41467-026-73856-w.
APA
Li Yang, Yu-Heng Zhou, Junya Hayase, Lei Wang, Weiguang Zhang, Erfei Bi, et al (2026). PAR3-mediated coordination of hepatocyte proliferation, maturation, and architecture in liver development and regeneration.. Nature communications. https://doi.org/10.1038/s41467-026-73856-w
GB/T 7714
Li Yang, Yu-Heng Zhou, Junya Hayase, Lei Wang, Weiguang Zhang, Erfei Bi, et al. PAR3-mediated coordination of hepatocyte proliferation, maturation, and architecture in liver development and regeneration.[J]. Nature communications, 2026 doi:10.1038/s41467-026-73856-w.
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