HOXC10 promotes hypertrophic scar fibroblast fibrosis through the regulation of STMN2 and the TGF-β/Smad signaling pathway.

IF 2.1 4区 生物学 Q4 CELL BIOLOGY
Histochemistry and Cell Biology Pub Date : 2024-11-01 Epub Date: 2024-08-16 DOI:10.1007/s00418-024-02317-6
Xin Zhou, Song Lin
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Abstract

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.

Abstract Image

HOXC10通过调控STMN2和TGF-β/Smad信号通路促进肥厚性瘢痕成纤维细胞纤维化。
增生性瘢痕(HS)的病理生理学与癌症有相似之处。HOXC10是一种与癌症发展密切相关的基因,它在HS中的表达水平高于正常皮肤(NS),这表明它在HS的调控中可能发挥作用。而HOXC10影响HS的确切功能和机制有待进一步明确。基因和蛋白质表达采用raeal-time定量聚合酶链反应(RT-qPCR)和Western印迹技术进行分析。使用 EdU 增殖试验、CCK-8 试验、划痕试验和 Transwell 试验评估了细胞的增殖和迁移。染色质免疫沉淀(ChIP)和双荧光素酶报告实验用于研究 HOXC10 和 STMN2 之间的相互作用。HS组织中HOXC10和STMN2的表达水平明显高于NS组织。沉默HOXC10会导致肥厚性瘢痕成纤维细胞(HSFs)的活化、增殖、迁移和纤维化减少。我们的研究结果还表明,HOXC10 直接靶向 STMN2。STMN2的过表达逆转了HOXC10敲除对HSF活化、增殖、迁移和纤维化的促进作用。我们进一步证实,HOXC10通过TGF-β/Smad信号通路调节HSF的活性。HOXC10通过促进STMN2的转录活化和TGF-β/Smad信号通路诱导HSF的活化和纤维化。这项研究表明,HOXC10可能是开发HS治疗方法的一个有前途的靶点。
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来源期刊
Histochemistry and Cell Biology
Histochemistry and Cell Biology 生物-细胞生物学
CiteScore
4.90
自引率
8.70%
发文量
112
审稿时长
1 months
期刊介绍: Histochemistry and Cell Biology is devoted to the field of molecular histology and cell biology, publishing original articles dealing with the localization and identification of molecular components, metabolic activities and cell biological aspects of cells and tissues. Coverage extends to the development, application, and/or evaluation of methods and probes that can be used in the entire area of histochemistry and cell biology.
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