Abstract：
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.
摘要：
增生性瘢痕（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具有抑制作用；然而，确切的机制尚不清楚。在这项研究中,我们旨在评估IFN-α2b对增生性瘢痕成纤维细胞（HSF）增殖和迁移的抑制作用，并进一步探讨相关的分子机制。细胞计数试剂盒-8和CyQUANT测定用于评估HSF的增殖；伤口愈合和Transwell测定用于评估HSF的迁移；实时定量聚合酶链反应和蛋白质印迹用于检测信使RNA和蛋白质水平，分别,相关基因；进行生物信息学分析以预测IFN-α2b的下游靶标。我们的发现如下：（1）IFN-α2b以剂量依赖性方式抑制HSF的增殖和迁移。(2)IFN-α2b通过抑制Wnt/β-catenin通路抑制HSF的增殖和迁移。(3)视黄酸受体应答者3(RARRES3)被预测为IFN-α2b的功能性下游分子,在HSF中很低。(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HSF的增殖和迁移。总之,IFN-α2b诱导的RARRES3上调通过Wnt/β-catenin通路抑制抑制HSF增殖和迁移。
