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微小RNA-138/过氧化物酶体增殖物激活受体β信号通路在体外调节人增生性瘢痕成纤维细胞的增殖与迁移。

MiR-138/peroxisome proliferator-activated receptor β signaling regulates human hypertrophic scar fibroblast proliferation and movement in vitro.

作者信息

Xiao Ying-ying, Fan Peng-ju, Lei Shao-rong, Qi Min, Yang Xing-hua

机构信息

Department of Plastic and Cosmetic Surgery, XiangYa Hospital, Central South University, Changsha, China.

出版信息

J Dermatol. 2015 May;42(5):485-95. doi: 10.1111/1346-8138.12792. Epub 2015 Mar 6.

DOI:10.1111/1346-8138.12792
PMID:25752881
Abstract

Excessive scars affect a patient's quality of life, both physically and psychologically, by causing pruritus, pain and contractures. Because there is a poor understanding of the complex mechanisms underlying the processes of hypertrophic scar formation, most therapeutic approaches remain clinically unsatisfactory. In this study, we found that miR-138 was downregulated and peroxisome proliferator-activated receptor (PPARβ) was inversely upregulated in hypertrophic scar tissues compared to in paired normal skin tissues. Using a dual-luciferase assay, we validated that miR138 directly targets PPARβ and regulates its expression at the transcriptional and translational levels. In gain-and-loss experiments, we found that miR-138/PPARβ signaling regulated human hypertrophic scar fibroblast proliferation and movement, and affected scarring-related protein expression, which suggests that miR-138/PPARβ signaling is important for hypertrophic scarring. Thus, our study provides evidence to help determine whether miR-138/PPARβ signaling may be a potential target for hypertrophic scarring management.

摘要

过度增生的瘢痕会导致瘙痒、疼痛和挛缩,从而在生理和心理上影响患者的生活质量。由于对肥厚性瘢痕形成过程背后的复杂机制了解不足,大多数治疗方法在临床上仍不能令人满意。在本研究中,我们发现与配对的正常皮肤组织相比,肥厚性瘢痕组织中miR-138表达下调,而过氧化物酶体增殖物激活受体(PPARβ)表达上调。通过双荧光素酶报告基因检测,我们验证了miR-138直接靶向PPARβ,并在转录和翻译水平上调节其表达。在功能获得和缺失实验中,我们发现miR-138/PPARβ信号通路调节人肥厚性瘢痕成纤维细胞的增殖和迁移,并影响瘢痕相关蛋白的表达,这表明miR-138/PPARβ信号通路对肥厚性瘢痕形成很重要。因此,我们的研究为确定miR-138/PPARβ信号通路是否可能成为肥厚性瘢痕治疗的潜在靶点提供了证据。

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