纤维化是稳定的细胞外基质（ECM）的过度沉积；纤维化组织主要由高度交联的 I 型胶原和高度收缩的肌成纤维细胞组成。系统性硬化症（SSc）是一种多系统自身免疫性结缔组织疾病，以皮肤和器官纤维化为特征。 40 多年前，人们就认识到 SSc 中的纤维化过程，但在改善肺部受累方面对 SSc 纤维化具有明显疗效的药物直到最近才被发现。不幸的是，这些治疗对于改善 SSc 患者的皮肤评分无效。先前的 SSc 临床试验主要集中在抗炎药物的交叉用途和移植领域免疫抑制药物的使用，以解决炎症和/或自身免疫过程。对通过直接靶向 SSc 中的 ECM 的能力而开发的特定抗纤维化药物进行了有限的检查，例如，通过减轻持续的基质硬度和机械转导，这可能是纤维化的起始和维持所需的，包括 SSc 中的纤维化。然而，由于 ECM 在 SSc 表型中的重要性，现在已经尝试确定专门针对 ECM 的药物，包括目前正在考虑用于治疗癌症的一些药物。© 2023。Springer Nature Limited。

Fibrosis is the excessive deposition of a stable extracellular matrix (ECM); fibrotic tissue is composed principally of highly crosslinked type I collagen and highly contractile myofibroblasts. Systemic sclerosis (SSc) is a multisystem autoimmune connective tissue disease characterized by skin and organ fibrosis. The fibrotic process has been recognized in SSc for >40 years, but drugs with demonstrable efficacy against SSc fibrosis in ameliorating the lung involvement have only recently been identified. Unfortunately, these treatments are ineffective at improving the skin score in patients with SSc. Previous clinical trials in SSc have largely focused on the cross-purposing of anti-inflammatory drugs and the use of immunosuppressive drugs from the transplantation field, which address inflammatory and/or autoimmune processes. Limited examination has taken place of specific anti-fibrotic agents developed through their ability to directly target the ECM in SSc by, for example, alleviating the persistent matrix stiffness and mechanotransduction that might be required for both the initiation and maintenance of fibrosis, including in SSc. However, because of the importance of the ECM in the SSc phenotype, attempts have now been made to identify drugs that specifically target the ECM, including some drugs that are currently under consideration for the treatment of cancer.© 2023. Springer Nature Limited.