Department of Medical Cosmetology, Xiangyang No.1 People's Hospital, Hubei University of Medicine, No. 15, Jiefang Road, Fancheng District, Xiangyang, 441000, Hubei, China.
Histochem Cell Biol. 2024 Nov;162(5):403-413. doi: 10.1007/s00418-024-02317-6. Epub 2024 Aug 16.
The pathophysiology of hypertrophic scar (HS) shares similarities with cancer. HOXC10, a gene significantly involved in cancer development, exhibits higher expression levels in HS than in normal skin (NS), suggesting its potential role in HS regulation. And the precise functions and mechanisms by which HOXC10 influences HS require further clarification. Gene and protein expressions were analyzed using raeal-time quantitative polymerase chain reaction (RT-qPCR) and western blot techniques. Cell proliferation and migration were evaluated using EdU proliferation assays, CCK-8 assays, scratch assays, and Transwell assays. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were conducted to investigate the interactions between HOXC10 and STMN2. HOXC10 and STMN2 expression levels were significantly higher in HS tissues compared with NS tissues. Silencing HOXC10 led to decreased activation, proliferation, migration, and fibrosis in hypertrophic scar fibroblasts (HSFs). Our findings also indicate that HOXC10 directly targets STMN2. The promotional effects of HOXC10 knockdown on HSF activation, proliferation, migration, and fibrosis were reversed by STMN2 overexpression. We further demonstrated that HOXC10 regulates HSF activity through the TGF-β/Smad signaling pathway. HOXC10 induces the activation and fibrosis of HSFs by promoting the transcriptional activation of STMN2 and engaging the TGF-β/Smad signaling pathway. This study suggests that HOXC10 could be a promising target for developing treatments for HS.
增生性瘢痕（HS）的病理生理学与癌症有相似之处。HOXC10 是一个在癌症发展中起重要作用的基因，在 HS 中的表达水平明显高于正常皮肤（NS），表明其在 HS 调控中可能起作用。HOXC10 影响 HS 的具体功能和机制仍需进一步阐明。采用实时定量聚合酶链反应（RT-qPCR）和 Western blot 技术分析基因和蛋白表达。通过 EdU 增殖试验、CCK-8 试验、划痕试验和 Transwell 试验评估细胞增殖和迁移。通过染色质免疫沉淀（ChIP）和双荧光素酶报告基因试验研究 HOXC10 与 STMN2 之间的相互作用。HOXC10 和 STMN2 在 HS 组织中的表达水平明显高于 NS 组织。沉默 HOXC10 可降低 HS 成纤维细胞（HSFs）的激活、增殖、迁移和纤维化。我们的研究结果还表明，HOXC10 可直接靶向 STMN2。STMN2 过表达可逆转 HOXC10 敲低对 HSF 激活、增殖、迁移和纤维化的促进作用。我们进一步证明，HOXC10 通过 TGF-β/Smad 信号通路调节 HSF 活性。HOXC10 通过促进 STMN2 的转录激活和参与 TGF-β/Smad 信号通路，诱导 HSFs 的激活和纤维化。这项研究表明，HOXC10 可能是治疗 HS 的一个有前途的靶点。
