基质凝血酶原 1 抑制口腔黏膜下纤维化的血管生成

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE International Journal of Oral Science Pub Date : 2024-02-26 DOI:10.1038/s41368-024-00286-z
Xiao Yang, Hui Zhao, Rui Li, Yang Chen, Zhi Xu, Zhengjun Shang
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引用次数: 0

摘要

口腔黏膜下纤维化(OSF)是一种主要由咀嚼槟榔诱发的恶性前疾病,其组织学特征是黏膜血管减少。然而,由于缺乏可用的模型,对 OSF 中血管生成的研究面临挑战。在这里,我们发现在 OSF 组织的基质中,内源性血管促进蛋白血栓形成蛋白 1(THBS1)的表达升高。利用成纤维细胞附着的类器官(FAO)模型,我们在体外稳定地再现了THBS1在OSF中的过表达。在 FAO 模型中,使用山苍子中的一种主要致病成分--山苍子碱处理可增强上皮细胞分泌转化生长因子 (TGF)-β1,从而促进成纤维细胞中 THBS1 的表达。此外,人脐静脉内皮细胞(HUVECs)也被加入到 FAO 中,以模拟血管成分。成纤维细胞中THBS1的过表达大大抑制了血管化FAO(vFAO)中内皮细胞的萌发能力。同样,用异甲唑啉处理会降低血管化 FAO 中 CD31 的表达,而当内皮细胞与 THBS1 受体 CD36 的中和抗体预孵育时,这种效应会减弱。最后,在arecoline诱导的大鼠OSF模型中,抑制THBS1可减轻胶原沉积和体内血管活力的下降。总之,我们利用组装的类器官模型研究了OSF的发病机制,并为靶向THBS1提供了理论依据。
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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Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis

A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model, treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-β1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs) were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (vFAOs). Consistently, treatment with arecoline reduced the expression of CD31 in vFAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.

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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
期刊最新文献
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