Shihata Waled A, Putra Mohammad R A, Chin-Dusting Jaye P F
Vascular Pharmacology Laboratory, Cardiovascular Disease Program, Department of Pharmacology, Biomedical Discovery Institute, Monash UniversityClayton, VIC, Australia.
Department of Medicine, Monash UniversityClayton, VIC, Australia.
Front Pharmacol. 2017 Aug 24;8:567. doi: 10.3389/fphar.2017.00567. eCollection 2017.
Fibrosis is a process of dysfunctional wound repair, described by a failure of tissue regeneration and excessive deposition of extracellular matrix, resulting in tissue scarring and subsequent organ deterioration. There are a broad range of stimuli that may trigger, and exacerbate the process of fibrosis, which can contribute to the growing rates of morbidity and mortality. Whilst the process of fibrosis is widely described and understood, there are no current standard treatments that can reduce or reverse the process effectively, likely due to the continuing knowledge gaps surrounding the cellular mechanisms involved. Several cellular targets have been implicated in the regulation of the fibrotic process including membrane domains, ion channels and more recently mechanosensors, specifically caveolae, particularly since these latter contain various signaling components, such as members of the TGFβ and MAPK/ERK signaling pathways, all of which are key players in the process of fibrosis. This review explores the anti-fibrotic influences of the caveola, and in particular the key underpinning protein, caveolin-1, and its potential as a novel therapeutic target.
纤维化是一种功能失调的伤口修复过程，其特征为组织再生失败和细胞外基质过度沉积，导致组织瘢痕形成及随后的器官功能恶化。有多种刺激因素可能引发并加剧纤维化过程，这会导致发病率和死亡率不断上升。虽然纤维化过程已得到广泛描述和理解，但目前尚无能够有效减轻或逆转该过程的标准治疗方法，这可能是由于围绕相关细胞机制仍存在知识空白。包括膜结构域、离子通道以及最近发现的机械传感器（特别是小窝）在内的多个细胞靶点都与纤维化过程的调控有关，尤其是因为后者包含多种信号成分，如转化生长因子β（TGFβ）和丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）信号通路的成员，所有这些都是纤维化过程中的关键参与者。本综述探讨了小窝的抗纤维化作用，特别是关键的基础蛋白小窝蛋白-1及其作为新型治疗靶点的潜力。
