J Clin Invest. 2018 Jan 2;128(1):85-96. doi: 10.1172/JCI93562.
Epithelial cell loss alters a tissue's optimal function and awakens evolutionarily adapted healing mechanisms to reestablish homeostasis. Although adult mammalian organs have a limited regeneration potential, the liver stands out as one remarkable exception. Following injury, the liver mounts a dynamic multicellular response wherein stromal cells are activated in situ and/or recruited from the bloodstream, the extracellular matrix (ECM) is remodeled, and epithelial cells expand to replenish their lost numbers. Chronic damage makes this response persistent instead of transient, tipping the system into an abnormal steady state known as fibrosis, in which ECM accumulates excessively and tissue function degenerates. Here we explore the cellular and molecular switches that balance hepatic regeneration and fibrosis, with a focus on uncovering avenues of disease modeling and therapeutic intervention.
上皮细胞丢失会改变组织的最佳功能，并激活进化适应的愈合机制以重新建立体内平衡。尽管成年哺乳动物器官的再生潜力有限，但肝脏是一个显著的例外。在损伤后，肝脏会引发一种动态的多细胞反应，其中基质细胞在原位被激活和/或从血液中招募，细胞外基质（ECM）被重塑，上皮细胞扩张以补充其丢失的数量。慢性损伤使这种反应持续存在而不是短暂的，使系统进入一种称为纤维化的异常稳定状态，其中 ECM 过度积累，组织功能退化。在这里，我们探讨了平衡肝再生和纤维化的细胞和分子开关，重点是发现疾病建模和治疗干预的途径。
