Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam, University of Amsterdam, The Netherlands.
Matrix Biol. 2013 Aug 8;32(6):307-15. doi: 10.1016/j.matbio.2013.03.005. Epub 2013 Apr 11.
Fibrosis underlies the pathogenesis of numerous diseases and leads to severe damage of vital body organs and, frequently, to death. Better understanding of the mechanisms resulting in fibrosis is essential for developing appropriate treatment solutions and is therefore of upmost importance. Recent evidence suggests a significant antifibrotic potential of an integral membrane protein, caveolin-1. While caveolin-1 has been widely studied for its role in the regulation of cell signaling and endocytosis, its possible implication in fibrosis remains largely unclear. In this review we survey involvement of caveolin-1 in various cellular processes and highlight different aspects of its antifibrotic activity. We hypothesize that caveolin-1 conveys a homeostatic function in the process of fibrosis by (a) regulating TGF-β1 and its downstream signaling; (b) regulating critical cellular processes involved in tissue repair, such as migration, adhesion and cellular response to mechanical stress; and (c) antagonizing profibrotic processes, such as proliferation. Finally, we consider this homeostatic function of caveolin-1 as a possible novel approach in treatment of fibroproliferative diseases.
纤维化是许多疾病的发病机制基础,会导致重要身体器官的严重损伤,并经常导致死亡。更好地了解导致纤维化的机制对于开发适当的治疗方案至关重要,因此具有最重要的意义。最近的证据表明,完整的膜蛋白窖蛋白-1 具有显著的抗纤维化潜力。尽管窖蛋白-1 因其在细胞信号转导和内吞作用中的调节作用而被广泛研究,但它在纤维化中的可能作用仍不清楚。在这篇综述中,我们调查了窖蛋白-1 在各种细胞过程中的参与情况,并强调了其抗纤维化活性的不同方面。我们假设窖蛋白-1 通过以下方式在纤维化过程中发挥着维持内稳态的功能:(a) 调节 TGF-β1 及其下游信号转导;(b) 调节组织修复过程中的关键细胞过程,如迁移、黏附和细胞对机械应激的反应;和 (c) 拮抗促纤维化过程,如增殖。最后,我们将窖蛋白-1 的这种内稳态功能视为治疗纤维增生性疾病的一种新的可能方法。