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自噬激活对于口腔黏膜愈合过程中的成肌纤维细胞分化是必需的。

Autophagy activation is required for myofibroblast differentiation during healing of oral mucosa.

机构信息

Department of Experimental Medicine, Sapienza University of Rome, Roma, Italy.

Section of Periodontology, Sapienza University of Rome, Roma, Italy.

出版信息

J Clin Periodontol. 2017 Oct;44(10):1039-1050. doi: 10.1111/jcpe.12767. Epub 2017 Aug 25.

Abstract

AIM

It is known that periodontal tissues heal faster that skin, and gingiva in particular heal without scar formation. The mechanisms regulating this behaviour are still unclear. The aim of our work was to compare wound healing in oral mucosa and gingiva, investigating the role of α-smooth muscle actin (αSMA)-expressing myofibroblasts and autophagy.

MATERIALS AND METHODS

Biopsies were obtained from seven patients immediately before and 24 hr after vertical releasing incision in oral mucosa and attached gingiva. Both whole biopsies and primary cultures of fibroblasts derived from the same tissues were subjected to immunofluorescence, Western blot and quantitative real-time PCR analyses.

RESULTS

We demonstrated that in oral mucosa, characterized by partially fibrotic outcome during repair, the activation of autophagy determined an increase in αSMA and collagen 1a1 production. Conversely, wound healing did not stimulate autophagy in attached gingiva, and subsequently, no increase in myofibroblast differentiation and collagen deposition could be seen, thus justifying its scarless outcome.

CONCLUSIONS

The elucidation of the differential regulation of autophagy in periodontal tissues and its correlation with myofibroblast differentiation and fibrotic outcome could allow the identification of new molecules involved in periodontal healing and the development of new surgical approaches for periodontal treatment that could improve the outcome of postoperative wounds.

摘要

目的

众所周知,牙周组织的愈合速度快于皮肤,尤其是牙龈可以无瘢痕愈合。但调控这一行为的机制仍不清楚。我们的工作旨在比较口腔黏膜和牙龈的愈合过程,研究α-平滑肌肌动蛋白(αSMA)表达的肌成纤维细胞和自噬的作用。

材料和方法

从 7 例患者的口腔黏膜和附着龈中,在垂直松弛切口前即刻和 24 小时后获取活检。对整个活检组织和源自同一组织的原代成纤维细胞培养物进行免疫荧光、Western blot 和定量实时 PCR 分析。

结果

我们证实,在口腔黏膜中,修复过程中表现为部分纤维化,自噬的激活导致 αSMA 和胶原 1a1 的产生增加。相反,附着龈中的伤口愈合并未刺激自噬,因此不会看到肌成纤维细胞分化和胶原沉积增加,从而解释了其无瘢痕愈合的结果。

结论

阐明牙周组织中自噬的差异调控及其与肌成纤维细胞分化和纤维化结果的相关性,可识别参与牙周愈合的新分子,并开发新的牙周治疗手术方法,从而改善术后伤口的预后。

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