Hypertrophic scar (HS) is a severe skin fibrotic disorder with unclear pathogenesis. Interferon-α2b (IFN-α2b) exerts inhibitory effects on HS in vivo and in vitro; however, the exact mechanism remains unclear. In this study, we aimed to evaluate the inhibitory effects of IFN-α2b on hypertrophic scar fibroblasts' (HSFs) proliferation and migration, and to further investigate the associated molecular mechanism. Cell Counting Kit-8 and CyQUANT assays were used to assess HSFs' proliferation; wound healing and Transwell assays were used to assess HSFs' migration; real-time quantitative polymerase chain reaction and Western blotting were used to detect messenger RNA and protein levels, respectively, of related genes; bioinformatics analysis was performed to predict the downstream target of IFN-α2b. Our findings are as follows: (1) IFN-α2b inhibited HSFs' proliferation and migration in a dose-dependent manner. (2) IFN-α2b inhibited HSFs' proliferation and migration by suppressing the Wnt/β-catenin pathway. (3) Retinoic-acid receptor responder 3 (RARRES3) was predicted as a functional downstream molecule of IFN-α2b, which was low in HSFs. (4) IFN-α2b inhibited HSF phenotypes and the Wnt/β-catenin pathway by upregulating RARRES3 expression. (5) RARRES3 restrained HSFs' proliferation and migration by repressing the Wnt/β-catenin pathway. In conclusion, IFN-α2b-induced RARRES3 upregulation inhibited HSFs' proliferation and migration through Wnt/β-catenin pathway suppression.

中文翻译：

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干扰素-α2b 诱导的 RARRES3 上调通过抑制 Wnt/β-连环蛋白通路抑制增生性瘢痕成纤维细胞的增殖和迁移

增生性疤痕 (HS) 是一种严重的皮肤纤维化疾病，发病机制尚不清楚。干扰素-α2b (IFN-α2b)在体内和体外对 HS 发挥抑制作用; 然而，确切的机制仍不清楚。在本研究中，我们旨在评估 IFN-α2b 对肥厚性瘢痕成纤维细胞 (HSFs) 增殖和迁移的抑制作用，并进一步研究相关的分子机制。Cell Counting Kit-8 和 CyQUANT 测定用于评估 HSF 的增殖；伤口愈合和 Transwell 检测用于评估 HSF 的迁移；采用实时定量聚合酶链反应和Western blotting分别检测相关基因的信使RNA和蛋白水平；进行生物信息学分析以预测 IFN-α2b 的下游靶标。我们的研究结果如下： (1) IFN-α2b 以剂量依赖的方式抑制 HSFs 的增殖和迁移。(2) IFN-α2b 抑制 HSFs' 通过抑制 Wnt/β-catenin 通路增殖和迁移。(3) 视黄酸受体反应器 3 (RARRES3) 被预测为 IFN-α2b 的功能性下游分子，其在 HSF 中含量较低。(4) IFN-α2b 通过上调 RARRES3 表达抑制 HSF 表型和 Wnt/β-catenin 通路。(5) RARRES3通过抑制Wnt/β-catenin通路抑制HSFs的增殖和迁移。总之，IFN-α2b 诱导的 RARRES3 上调通过抑制 Wnt/β-catenin 通路抑制 HSF 的增殖和迁移。通过抑制 Wnt/β-catenin 通路增殖和迁移。总之，IFN-α2b 诱导的 RARRES3 上调通过抑制 Wnt/β-catenin 通路抑制 HSF 的增殖和迁移。通过抑制 Wnt/β-catenin 通路增殖和迁移。总之，IFN-α2b 诱导的 RARRES3 上调通过抑制 Wnt/β-catenin 通路抑制 HSF 的增殖和迁移。