Title:The Role of Pro-fibrotic Myofibroblasts in Systemic Sclerosis: From Origin to Therapeutic Targeting
Volume: 22
Issue: 3
关键词:
系统性硬化症、硬皮病、纤维化、肌成纤维细胞、信号通路、治疗靶点
摘要: Systemic sclerosis (SSc, scleroderma) is a complex connective tissue
disorder characterized by multisystem clinical manifestations resulting from immune
dysregulation/autoimmunity, vasculopathy, and, most notably, progressive fibrosis of the
skin and internal organs. In recent years, it has been observed that the main drivers of
SSc-related tissue fibrosis are myofibroblasts, a type of mesenchymal cells with both the
extracellular matrix-synthesizing features of fibroblasts and the cytoskeletal
characteristics of contractile smooth muscle cells. The accumulation and persistent
activation of pro-fibrotic myofibroblasts during SSc development and progression result
in elevated mechanical stress and reduced matrix plasticity within the affected tissues
and may be ascribed to a reduced susceptibility of these cells to pro-apoptotic stimuli, as
well as their increased formation from tissue-resident fibroblasts or transition from
different cell types. Given the crucial role of myofibroblasts in SSc pathogenesis, finding
the way to inhibit myofibroblast differentiation and accumulation by targeting their
formation, function, and survival may represent an effective approach to hamper the
fibrotic process or even halt or reverse established fibrosis. In this review, we discuss
the role of myofibroblasts in SSc-related fibrosis, with a special focus on their cellular
origin and the signaling pathways implicated in their formation and persistent activation.
Furthermore, we provide an overview of potential therapeutic strategies targeting
myofibroblasts that may be able to counteract fibrosis in this pathological condition.
