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β-榄香烯通过激活人增生性瘢痕成纤维细胞中的P53途径诱导细胞凋亡。

β-Elemene induces apoptosis by activating the P53 pathway in human hypertrophic scar fibroblasts.

作者信息

Guo Qin, Li Yujia, Chen Yuan, Ji Jin, Zheng Shizhong, Xu Xuefen, Zhang Biyun, Ye Jianzhou

机构信息

Department of Dermatology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

IUBMB Life. 2022 Jun;74(6):508-518. doi: 10.1002/iub.2614. Epub 2022 Mar 28.

Abstract

Hypertrophic scar (HS) is a condition characterized by excessive synthesis and deposition of collagen. There are many clinical methods to alleviate HS, but most of them are accompanied by many complications. To investigate the effects of β-Elemene, extracted from the ginger family plant Wenyujin, on human hypertrophic scar fibroblast (hHSFs). Cultured hHSFs and human normal fibroblasts, observed the effect of β-Elemene on apoptosis, extracellular matrix, and endoplasmic reticulum stress (ERS) by western blot, Real Time-Polymerase Chain Reaction (RT-PCR), and flow cytometry. Based on our findings, it is clear that β-Elemene could inhibit the expression of α-smooth muscle actin (α-SMA), collagen I, and fibronectin, reduced collagen deposition. Further studies had found that β-Elemene could increase the expression of ERS-related proteins CHOP and Calnexin in a dose-dependent manner, thereby promoting the aggregation of cleaved-caspase-3 and inducing hHSFs to undergo poptosis. This process may depend on the regulation of P53. The results of our study indicates that β-Elemene induced hHSFs to undergo apoptosis though ERS pathway in a P53-dependent manner, which means that our research provided a new strategy for the development of drugs for the treatment of HS.

摘要

增生性瘢痕(HS)是一种以胶原蛋白过度合成和沉积为特征的病症。有许多临床方法可缓解HS,但其中大多数都伴有许多并发症。为了研究从姜科植物温郁金中提取的β-榄香烯对人增生性瘢痕成纤维细胞(hHSFs)的影响。培养hHSFs和人正常成纤维细胞,通过蛋白质免疫印迹法、实时聚合酶链反应(RT-PCR)和流式细胞术观察β-榄香烯对细胞凋亡、细胞外基质和内质网应激(ERS)的影响。根据我们的研究结果,很明显β-榄香烯可以抑制α-平滑肌肌动蛋白(α-SMA)、胶原蛋白I和纤连蛋白的表达,减少胶原蛋白沉积。进一步研究发现,β-榄香烯可以剂量依赖性方式增加ERS相关蛋白CHOP和钙连接蛋白的表达,从而促进裂解的半胱天冬酶-3的聚集并诱导hHSFs发生凋亡。这个过程可能依赖于P53的调节。我们的研究结果表明,β-榄香烯通过ERS途径以P53依赖的方式诱导hHSFs凋亡,这意味着我们的研究为开发治疗HS的药物提供了一种新策略。

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