Fibrotic tissue remodelling and vascular alterations cause high morbidity and mortality in patients with systemic sclerosis (SSc).1 2 While the pathogenesis of SSc is only partially understood, recent evidence demonstrates a fundamental role of hedgehog signalling in fibrotic disease manifestations. Hedgehog signalling is activated in fibrotic SSc skin, and it induces an SSc-like phenotype in resting fibroblasts.3 Overexpression of sonic hedgehog (SHH) induces skin fibrosis, whereas inhibition of hedgehog signalling ameliorates experimental fibrosis.4 Based on these experimental findings, this European Scleroderma Trials and Research group (EUSTAR) multicentre cooperative study investigates whether circulating SHH may serve as a surrogate marker for a more severe disease phenotype in patients with SSc. We decided to evaluate SHH serum levels rather than total circulating SHH. Measurements of SHH serum levels are easy and robust but may not assess particulated SHH in various different extracellular vesicles. …

中文翻译：

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超声刺猬血清水平升高与系统性硬化症中的纤维化和血管表现有关

纤维化组织重塑和血管改变导致系统性硬化症 (SSc) 患者的高发病率和死亡率。1 2 虽然仅部分了解 SSc 的发病机制，但最近的证据表明，hedgehog 信号传导在纤维化疾病表现中具有重要作用。Hedgehog 信号在纤维化 SSc 皮肤中被激活，并在静息成纤维细胞中诱导 SSc 样表型。3 声波刺猬 (SHH) 的过度表达诱导皮肤纤维化，而刺猬信号的抑制可改善实验性纤维化。4 基于这些实验结果，这欧洲硬皮病试验和研究组 (EUSTAR) 多中心合作研究调查循环 SHH 是否可以作为 SSc 患者更严重疾病表型的替代标志物。我们决定评估 SHH 血清水平而不是总循环 SHH。SHH 血清水平的测量既简单又可靠，但可能无法评估各种不同细胞外囊泡中的微粒 SHH。…