Friedman Scott L
Division of Liver Diseases, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
Physiol Rev. 2008 Jan;88(1):125-72. doi: 10.1152/physrev.00013.2007.
The hepatic stellate cell has surprised and engaged physiologists, pathologists, and hepatologists for over 130 years, yet clear evidence of its role in hepatic injury and fibrosis only emerged following the refinement of methods for its isolation and characterization. The paradigm in liver injury of activation of quiescent vitamin A-rich stellate cells into proliferative, contractile, and fibrogenic myofibroblasts has launched an era of astonishing progress in understanding the mechanistic basis of hepatic fibrosis progression and regression. But this simple paradigm has now yielded to a remarkably broad appreciation of the cell's functions not only in liver injury, but also in hepatic development, regeneration, xenobiotic responses, intermediary metabolism, and immunoregulation. Among the most exciting prospects is that stellate cells are essential for hepatic progenitor cell amplification and differentiation. Equally intriguing is the remarkable plasticity of stellate cells, not only in their variable intermediate filament phenotype, but also in their functions. Stellate cells can be viewed as the nexus in a complex sinusoidal milieu that requires tightly regulated autocrine and paracrine cross-talk, rapid responses to evolving extracellular matrix content, and exquisite responsiveness to the metabolic needs imposed by liver growth and repair. Moreover, roles vital to systemic homeostasis include their storage and mobilization of retinoids, their emerging capacity for antigen presentation and induction of tolerance, as well as their emerging relationship to bone marrow-derived cells. As interest in this cell type intensifies, more surprises and mysteries are sure to unfold that will ultimately benefit our understanding of liver physiology and the diagnosis and treatment of liver disease.
在超过130年的时间里，肝星状细胞一直令生理学家、病理学家和肝病学家感到惊讶并备受关注。然而，直到其分离和鉴定方法得到完善，其在肝损伤和纤维化中的作用才获得明确证据。肝损伤中静止的富含维生素A的星状细胞激活成为增殖、收缩和纤维化的肌成纤维细胞这一范式，开启了在理解肝纤维化进展和消退的机制基础方面取得惊人进展的时代。但现在，这个简单的范式已让位于对该细胞功能的更广泛认识，其功能不仅涉及肝损伤，还包括肝脏发育、再生、异生素反应、中间代谢和免疫调节。最令人兴奋的前景之一是，星状细胞对肝祖细胞的扩增和分化至关重要。同样引人入胜的是星状细胞显著的可塑性，不仅体现在其可变的中间丝表型上，还体现在其功能上。星状细胞可被视为复杂肝血窦环境中的枢纽，这需要严格调控的自分泌和旁分泌相互作用、对不断变化的细胞外基质含量的快速反应，以及对肝脏生长和修复所带来的代谢需求的精确响应。此外，对全身稳态至关重要的作用包括它们对视黄醇的储存和动员、新出现的抗原呈递和诱导耐受的能力，以及它们与骨髓来源细胞的新关系。随着对这种细胞类型的兴趣不断增加，肯定会有更多的惊喜和谜团被揭开，这最终将有助于我们理解肝脏生理学以及肝病的诊断和治疗。
