Fibrosis can be defined as an excessive and deregulated deposition of extracellular matrix proteins, causing loss of physiological architecture and dysfunction of different tissues and organs. In the skin, fibrosis represents the hallmark of several acquired (e.g. systemic sclerosis and hypertrophic scars) and inherited (i.e. dystrophic epidermolysis bullosa) diseases. A complex series of interactions among a variety of cellular types and a wide range of molecular players drive the fibrogenic process, often in a context-dependent manner. However, the pathogenetic mechanisms leading to skin fibrosis are not completely elucidated. In this scenario, an increasing body of evidence has recently disclosed the involvement of Notch signalling cascade in fibrosis of the skin and other organs. Despite its apparent simplicity, Notch represents one of the most multifaceted, strictly regulated and intricate pathways with still unknown features both in health and disease conditions. Starting from the most recent advances in Notch activation and regulation, this review focuses on the pro-fibrotic function of Notch pathway in fibroproliferative skin disorders describing molecular networks, interplay with other pro-fibrotic molecules and pathways, including the transforming growth factor-β1, and therapeutic strategies under development.

中文翻译：

---

补充皮肤纤维化分子机制的知识：关注多方面的 Notch 信号通路

纤维化可以定义为细胞外基质蛋白过度和失调的沉积，导致生理结构的丧失和不同组织和器官的功能障碍。在皮肤中，纤维化代表了几种获得性（例如系统性硬化症和肥厚性疤痕）和遗传性（即营养不良性大疱性表皮松解症）疾病的标志。各种细胞类型和广泛的分子参与者之间的一系列复杂的相互作用通常以依赖于环境的方式驱动纤维化过程。然而，导致皮肤纤维化的发病机制尚未完全阐明。在这种情况下，最近越来越多的证据揭示了 Notch 信号级联参与皮肤和其他器官的纤维化。尽管看似简单，Notch 代表了最多方面、最严格监管和最复杂的途径之一，其在健康和疾病状况方面的特征仍然未知。从 Notch 激活和调节的最新进展开始，本综述重点关注 Notch 通路在描述分子网络的纤维增生性皮肤病中的促纤维化功能，与其他促纤维化分子和通路的相互作用，包括转化生长因子-β1，和正在开发的治疗策略。