Decreased serum cathepsin S levels in patients with systemic sclerosis-associated interstitial lung disease.
Decreased serum cathepsin S levels in patients with systemic sclerosis-associated interstitial lung disease.
复制标题
系统性硬化症相关间质性肺病患者血清组织蛋白酶 S 水平降低。
DOI：
10.1111/1346-8138.15458
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Asano Y.
中科院分区：
文献类型：
--
作者：
Toyama S;Yamashita T;Saigusa R;Miura S;Nakamura K;Hirabayashi M;Miyagawa T;Fukui Y;Omatsu J;Yoshizaki A;Sato S;Asano Y.
组织蛋白酶 S (CTSS) 是一种溶酶体蛋白水解酶，调节细胞内和细胞外生物活性，包括免疫/炎症以及脉管系统和细胞外基质的重塑，这是与系统性硬化症 (SSc) 相关的三个主要病理事件。为了阐明 CTSS 在 SSc 发展中的潜在作用，我们研究了血清 CTSS 水平的临床相关性。由于肾功能不全的 SSc 患者（eGFR，<60 min/mL/1.73 m2）血清 CTSS 水平与估计肾小球滤过率（eGFR）呈负相关，因此对肾功能正常的 SSc 患者（eGFR，≥60 min/mL/1.73 m2）进行分析。与局限性皮肤 SSc 患者和健康对照相比，弥漫性皮肤 SSc 患者的血清 CTSS 水平显着降低。在血管和纤维化临床表现中，雷诺现象和间质性肺疾病（ILD）与血清 CTSS 水平显着降低有关。重要的是，血清 CTSS 水平与总 SSc 患者的血清 Krebs von den Lungen-6 和表面活性蛋白 D 水平呈负相关，而与改良的 Rodnan 皮肤总厚度评分和一氧化碳预测扩散肺活量百分比不相关，与预测肺活量百分比呈正趋势。这些结果表明 CTSS 表达减少可能对 SSc 患者 ILD 的发展有贡献。
Cathepsin S (CTSS) is a lysosomal proteolytic enzyme regulating intracellular and extracellular biological activities, including immunity/inflammation and remodeling of vasculature and extracellular matrix, which are the three cardinal pathological events associated with systemic sclerosis (SSc). To elucidate the potential role of CTSS in the development of SSc, we investigated the clinical correlation of serum CTSS levels. Because serum CTSS levels were inversely correlated with estimated glomerular filtration rate (eGFR) in SSc patients with renal dysfunction (eGFR, <60 min/mL per 1.73 m2), SSc patients with normal renal function (eGFR, ≥60 min/mL per 1.73 m2) were analyzed. Serum CTSS levels were significantly decreased in diffuse cutaneous SSc patients compared with limited cutaneous SSc patients and healthy controls. Among vascular and fibrotic clinical manifestations, Raynaud’s phenomenon and interstitial lung disease (ILD) were relevant to a significant decrease in serum CTSS levels. Importantly, serum CTSS levels negatively correlated with serum levels of Krebs von den Lungen‐6 and surfactant protein D in total SSc patients, while not correlating with modified Rodnan total skin thickness score and the percentage of predicted diffusion lung capacity for carbon monoxide and showing a positive trend with the percentage of predicted vital capacity. These results suggest a potential contribution of decreased CTSS expression to the development of ILD in patients with SSc.