PDF(Pubmed)
Abstract：
UNASSIGNED: Oral submucosal fibrosis (OSF) is a premalignant disorder positively associated with betel nut chewing. Recent studies supported the promising benefits of histone deacetylase (HDAC) inhibitors for fibrosis treatment. Here we aim to clarify the pro-fibrogenic role of HDAC9 in regulating OSF.
UNASSIGNED: Healthy and OSF specimens were collected to investigate the clinical significance of HDAC9. Chronic arecoline treatment process was used to induce arecoline-mediated myofibroblasts-related activation of primary buccal mucosa fibroblasts (BMFs). Functional analysis of collagen gel contraction, transwell migration, and wound-healing assays were performed to assess the change in pro-fibrogenic properties of BMFs and fibrotic BMFs (fBMFs). Lentiviral-mediated HDAC9 knockdown was used to verify the role of HDAC9 in the pro-fibrogenic process.
UNASSIGNED: We found that arecoline significantly increased the mRNA and protein expression of HDAC9 of BMFs in a dose-dependent manner. Knockdown of HDAC9 in BMFs reversed the strengthened effects of arecoline on collagen gel contraction, cell migration, and wound-healing ability. We further demonstrated that knockdown of HDAC9 in fBMFs significantly attenuated its inherent pro-fibrogenic properties. Furthermore, we confirmed a significantly increased expression of HDAC9 mRNA in OSF compared to normal tissues, which suggested a positive correlation between the up-regulation of HDAC9 and OSF.
UNASSIGNED: We demonstrated that silencing of HDAC9 inhibited arecoline-induced activation and inherent pro-fibrogenic properties, suggesting potential therapeutics by targeting HDAC9 in the OSF treatment.
UNASSIGNED: Healthy and OSF specimens were collected to investigate the clinical significance of HDAC9. Chronic arecoline treatment process was used to induce arecoline-mediated myofibroblasts-related activation of primary buccal mucosa fibroblasts (BMFs). Functional analysis of collagen gel contraction, transwell migration, and wound-healing assays were performed to assess the change in pro-fibrogenic properties of BMFs and fibrotic BMFs (fBMFs). Lentiviral-mediated HDAC9 knockdown was used to verify the role of HDAC9 in the pro-fibrogenic process.
UNASSIGNED: We found that arecoline significantly increased the mRNA and protein expression of HDAC9 of BMFs in a dose-dependent manner. Knockdown of HDAC9 in BMFs reversed the strengthened effects of arecoline on collagen gel contraction, cell migration, and wound-healing ability. We further demonstrated that knockdown of HDAC9 in fBMFs significantly attenuated its inherent pro-fibrogenic properties. Furthermore, we confirmed a significantly increased expression of HDAC9 mRNA in OSF compared to normal tissues, which suggested a positive correlation between the up-regulation of HDAC9 and OSF.
UNASSIGNED: We demonstrated that silencing of HDAC9 inhibited arecoline-induced activation and inherent pro-fibrogenic properties, suggesting potential therapeutics by targeting HDAC9 in the OSF treatment.
摘要：
■口腔粘膜下纤维化（OSF）是一种与槟榔咀嚼呈正相关的癌变前疾病。最近的研究支持组蛋白去乙酰化酶（HDAC）抑制剂用于纤维化治疗的有希望的益处。在这里，我们旨在阐明HDAC9在调节OSF中的促纤维化作用。
■收集健康和OSF标本以研究HDAC9的临床意义。慢性槟榔碱处理过程用于诱导槟榔碱介导的肌成纤维细胞相关的原代颊粘膜成纤维细胞（BMF）的激活。胶原蛋白凝胶收缩的功能分析，Transwell迁移,进行和伤口愈合测定以评估BMF和纤维化BMF(fBMF)的促纤维化性质的变化。慢病毒介导的HDAC9敲低用于验证HDAC9在促纤维化过程中的作用。
■我们发现槟榔碱以剂量依赖的方式显着增加了BMF的HDAC9的mRNA和蛋白表达。BMF中HDAC9的敲除逆转了槟榔碱对胶原凝胶收缩的增强作用，细胞迁移，和伤口愈合能力。我们进一步证明了fBMF中HDAC9的敲低显著减弱了其固有的促纤维化特性。此外，我们证实了HDAC9mRNA在OSF中的表达显著高于正常组织,这表明HDAC9的上调与OSF之间存在正相关。
■我们证明了HDAC9的沉默抑制了槟榔碱诱导的活化和固有的促纤维化特性，通过在OSF治疗中靶向HDAC9提出潜在的治疗方法。
■收集健康和OSF标本以研究HDAC9的临床意义。慢性槟榔碱处理过程用于诱导槟榔碱介导的肌成纤维细胞相关的原代颊粘膜成纤维细胞（BMF）的激活。胶原蛋白凝胶收缩的功能分析，Transwell迁移,进行和伤口愈合测定以评估BMF和纤维化BMF(fBMF)的促纤维化性质的变化。慢病毒介导的HDAC9敲低用于验证HDAC9在促纤维化过程中的作用。
■我们发现槟榔碱以剂量依赖的方式显着增加了BMF的HDAC9的mRNA和蛋白表达。BMF中HDAC9的敲除逆转了槟榔碱对胶原凝胶收缩的增强作用，细胞迁移，和伤口愈合能力。我们进一步证明了fBMF中HDAC9的敲低显著减弱了其固有的促纤维化特性。此外，我们证实了HDAC9mRNA在OSF中的表达显著高于正常组织,这表明HDAC9的上调与OSF之间存在正相关。
■我们证明了HDAC9的沉默抑制了槟榔碱诱导的活化和固有的促纤维化特性，通过在OSF治疗中靶向HDAC9提出潜在的治疗方法。
