Galectin-9 is a β-galactoside-binding protein with two carbohydrate recognition domains. Recent studies have revealed that galectin-9 regulates cellular biological reactions and plays a pivotal role in fibrosis. The aim of this study was to determine the role of galectin-9 in the pathogenesis of bleomycin-induced systemic sclerosis (SSc). Human galectin-9 levels in the serum of patients with SSc and mouse sera galectin-9 levels were measured by a Bio-Plex immunoassay and enzyme-linked immunosorbent assay. Lung fibrosis was induced using bleomycin in galectin-9 wild-type and knockout mice. The effects of galectin-9 on the fibrosis markers and signaling molecules in the mouse lung tissues and primary lung fibroblast cells were assessed with western blotting and quantitative polymerase chain reaction. Galectin-9 levels in the serum were significantly higher (9-fold) in patients compared to those of healthy individuals. Galectin-9 deficiency in mice prominently ameliorated epithelial proliferation, collagen I accumulation, and α-smooth muscle actin expression. In addition, the galectin-9 knockout mice showed reduced protein expression levels of fibrosis markers such as Smad2/3, connective tissue growth factor, and endothelin-1. Differences between the wild-type and knockout groups were also observed in the AKT, mitogen-activated protein kinase, and c-Jun N-terminal kinase signaling pathways. Galectin-9 deficiency decreased the signal activation induced by transforming growth factor-beta in mouse primary fibroblasts, which plays a critical role in fibroblast activation and aberrant catabolism of the extracellular matrix. Our findings suggest that lack of galectin-9 protects against bleomycin-induced SSc. Moreover, galectin-9 might be involved in regulating the progression of fibrosis in multiple pathways.

中文翻译：

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通过TGF-β诱导的Sgal和非Smad信号转导途径改善galectin-9缺陷小鼠和成纤维细胞中博来霉素诱导的肺纤维化

Galectin-9是具有两个碳水化合物识别域的β-半乳糖苷结合蛋白。最近的研究表明，galectin-9调节细胞生物学反应，并在纤维化中起关键作用。这项研究的目的是确定galectin-9在博来霉素诱导的系统性硬化症（SSc）发病机理中的作用。通过Bio-Plex免疫测定和酶联免疫吸附测定法测量SSc患者血清中人半乳糖凝集素9水平和小鼠血清半乳糖凝集素9水平。使用博来霉素在galectin-9野生型和基因敲除小鼠中诱导肺纤维化。通过western印迹和定量聚合酶链反应评估了galectin-9对小鼠肺组织和原代肺成纤维细胞中纤维化标志物和信号分子的影响。与健康个体相比，患者血清中的Galectin-9水平明显更高（9倍）。小鼠的Galectin-9缺乏症可明显改善上皮增殖，胶原I积累和α-平滑肌肌动蛋白表达。此外，galectin-9基因敲除小鼠的纤维化标记物（如Smad2 / 3，结缔组织生长因子和内皮素-1）的蛋白表达水平降低。在AKT，有丝分裂原激活的蛋白激酶和c-Jun N端激酶信号通路中也观察到了野生型和基因敲除组之间的差异。Galectin-9缺乏症降低了小鼠原代成纤维细胞中转化生长因子-β诱导的信号激活，这在成纤维细胞激活和细胞外基质的异常分解代谢中起关键作用。我们的发现表明，缺乏半乳凝素9可以预防博来霉素诱导的SSc。此外，galectin-9可能参与多种途径调节纤维化的进程。