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Mechanism investigation of signal transduction on scar tissue formation of palatal mucosa

腭黏膜疤痕组织形成的信号转导机制研究

基本信息

批准号：
15592157
负责人：
BABA Yoshiyuki
金额：
$ 2.24万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15592157/
关键词：
palatal mucosa scar tissue organ culture alpha-smooth muscle FGFR TGF-β1 TGF-β1

项目摘要

The purpose of studies was, 1.establishment of the organ culture system for the investigation of rat palatal wound hearing model, and, 2.mechanism investigation of signal transduction of SMAD and ASK-1 mediated differentiation from fibroblasts into myofibroblasts.1.In order to establishing an in vitro organ culture model, after excision of palatal mucoperiosteum, explants from the developing immature scar tissue and from the normal palatal mucosa were used to observe myofibroblasts in vivo. The optimal culture condition was confirmed that xplants were cultured in the gas-liquid interface in serum-free Waymouth's MB 752/1 medium and in a humid atmosphere containing 55%O2/5%CO2 at 37 ℃. These results demonstrate that the established model provides a useful in vitro experimental tool for further investigation.2.Fibroblast growth factors (FGFs) regulate cell growth and differentiation and play crucial roles in the process of tissue repair and remodeling. We have previously shown that basic FGF is widely expressed at the injured site. Since the presence of FGF receptors (FGFRS) determines cellular responsiveness, we examined the localization of FGFR1, FGFR2 and FGFR3 expression by immunohistochemistry throughout the repair of full thickness excisional wounds up to 28 days after wounding. Strong expression of FGFR1 was observed in the nuclei of myofibroblasts, which are characterized by α-smooth muscle (α-SM) actin expression. The weak expression of FGFR2 was also observed in the nuclei of myofibroblasts. In contrast, there was no staining for FGFR3 in fibroblasts through the wound healing process. In addition, transforming growth factor-β1 (TGF-β1), a potential inducer of myofibroblasts, enhanced the expression of FGFR1 and FGFR2 in the nuclei of palatal fibroblasts in vitro. These findings suggest that FGFR1 and FGFR2 in myofibroblasts may be responsible for the signal transduction of FGF during the wound healing process.

本研究的目的是：1.建立大鼠腭创伤听力模型的器官培养体系; 2.探讨SMAD和ASK-1介导成纤维细胞向肌成纤维细胞分化的信号转导机制。从发育中的未成熟瘢痕组织和正常腭粘膜中取出的外植体用于观察体内的肌成纤维细胞。最佳培养条件为：气液界面培养，无血清Waymouth ′ s MB 752/1培养基，37 ℃，55%O_2/5%CO_2。这些结果表明，所建立的模型为进一步的研究提供了一个有用的体外实验工具。2.成纤维细胞生长因子（FGF）调节细胞的生长和分化，在组织修复和重塑过程中起着至关重要的作用。我们以前已经表明，碱性成纤维细胞生长因子在损伤部位广泛表达。由于FGF受体（FGFRS）的存在决定了细胞的反应性，我们通过免疫组化检查了FGFR 1，FGFR 2和FGFR 3表达的定位，在创伤后长达28天的全层切除伤口的修复过程中。在肌成纤维细胞的细胞核中观察到FGFR 1的强表达，其特征在于α-平滑肌（α-SM）肌动蛋白表达。FGFR 2在肌成纤维细胞核中也有弱表达。相反，在伤口愈合过程中成纤维细胞中没有FGFR 3染色。此外，肌成纤维细胞的诱导因子转化生长因子β1（TGF-β1）在体外可促进腭部成纤维细胞核内FGFR 1和FGFR 2的表达。这些结果表明，FGFR 1和FGFR 2在肌成纤维细胞可能是负责在伤口愈合过程中的FGF的信号转导。