Knockdown of Notch Suppresses Epithelial-mesenchymal Transition and Induces Angiogenesis in Oral Submucous Fibrosis by Regulating TGF-β1

IF 2.1 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical Genetics Pub Date : 2023-08-01 DOI:10.1007/s10528-023-10452-3

Jinrong Wang, Liyan Yang, Jie Mei, Zhixin Li, Yuqi Huang, Honglan Sun, Kaiyue Zheng, Huifang Kuang, Wen Luo

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引用次数: 0

Abstract

Oral submucous fibrosis (OSF) is a chronic disorder with a high malignant transformation rate. Epithelial-mesenchymal transition (EMT) and angiogenesis are key events in OSF. The Notch signaling plays an essential role in the pathogenesis of various fibrotic diseases, including OSF. Our study aimed to explore the effects of Notch on the EMT and angiogenesis processes during the development of OSF. The expression of Notch in OSF tissues versus normal buccal mucosa samples was compared. Arecoline was used to induce myofibroblast transdifferentiation of buccal mucosal fibroblasts (BMFs). Short hairpin RNA technique was used to knockdown Notch in BMFs. Pirfenidone and SRI-011381 were used to inhibit and activate the TGF-β1 signaling pathway in BMFs, respectively. The expression of Notch was markedly upregulated in OSF tissues and fibrotic BMFs. Knockdown of Notch significantly decreased the viability and promoted apoptosis in BMFs subjected to arecoline stimulation. Downregulation of Notch also significantly suppressed the EMT process, as shown by the reduction of N-cadherin and vimentin with concomitant upregulation of E-cadherin. In addition, knockdown of Notch upregulated VEGF and enhanced the angiogenic activity of fBMFs. Moreover, inhibition of TGF-β1 suppressed viability and EMT, promoted apoptosis, and induced angiogenesis of fBMFs, while activation of TGF-β1 significantly diminished the effects of Notch knockdown on fBMFs. Knockdown of Notch suppressed EMT and induced angiogenesis in OSF by regulating TGF-β1, suggesting that the Notch-TGF-β1 pathway may serve as a therapeutic intervention target for OSF.

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通过调节 TGF-β1 敲除 Notch 抑制上皮-间质转化并诱导口腔黏膜下纤维化的血管生成

口腔黏膜下纤维化（OSF）是一种恶性转化率很高的慢性疾病。上皮-间质转化（EMT）和血管生成是口腔黏膜下纤维化的关键事件。Notch信号在包括OSF在内的各种纤维化疾病的发病机制中起着至关重要的作用。我们的研究旨在探讨Notch对OSF发病过程中EMT和血管生成过程的影响。我们比较了 Notch 在 OSF 组织和正常颊粘膜样本中的表达。用阿瑞考林诱导颊粘膜成纤维细胞（BMFs）发生肌成纤维细胞转分化。采用短发夹 RNA 技术敲除 BMFs 中的 Notch。吡非尼酮和 SRI-011381 分别用于抑制和激活 BMFs 的 TGF-β1 信号通路。在OSF组织和纤维化的BMFs中，Notch的表达明显上调。敲除Notch可明显降低异甲唑啉刺激下BMF的活力并促进其凋亡。Notch的下调还能明显抑制EMT过程，表现为N-钙粘蛋白和波形蛋白的减少以及E-钙粘蛋白的上调。此外，敲除 Notch 会上调血管内皮生长因子，增强 fBMFs 的血管生成活性。此外，抑制 TGF-β1 可抑制 fBMFs 的活力和 EMT、促进细胞凋亡并诱导血管生成，而激活 TGF-β1 则可显著降低 Notch 敲除对 fBMFs 的影响。敲除Notch可通过调节TGF-β1抑制OSF的EMT并诱导血管生成，这表明Notch-TGF-β1通路可作为OSF的治疗干预靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochemical Genetics 生物-生化与分子生物学

CiteScore

3.90

自引率

0.00%

发文量

133

审稿时长

4.8 months

期刊介绍： Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.