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[6]-姜烯酚对转化生长因子-β1诱导的鼻息肉衍生成纤维细胞中肌成纤维细胞分化的影响。

Effect of [6]-gingerol on myofibroblast differentiation in transforming growth factor beta 1-induced nasal polyp-derived fibroblasts.

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, Guro Hospital, Korea University College of Medicine, Seoul, South Korea.

出版信息

Am J Rhinol Allergy. 2012 Mar-Apr;26(2):97-103. doi: 10.2500/ajra.2012.26.3736.

DOI:10.2500/ajra.2012.26.3736
PMID:22487285
Abstract

BACKGROUND

[6]-Gingerol is one of the major pungent principles of ginger and has diverse effects, including anti-inflammatory, and antioxidative effects. Reactive oxygen species (ROS) are released during the phenotypic transformation of fibroblasts to myofibroblasts, a process that is involved in the growth of nasal polyps by inducing extracellular matrix (ECM) accumulation. The purpose of this study was to determine the effect of [6]-gingerol on myofibroblast differentiation and collagen production of nasal polyp-derived fibroblasts (NPDFs) and to determine if the effect of [6]-gingerol is linked to an antioxidant effect.

METHODS

NPDFs were incubated and treated with transforming growth factor (TGF) beta 1. The ROS generated by NPDFs were determined using 2″,7″-dichlorfluorescein-diacetate. The fluorescence was captured by a fluorescent microscope and measured using a fluorometer. The expression of alpha-smooth muscle actin (SMA) and collagen type IV mRNA was determined by a reverse transcription-polymerase chain reaction, and the expression of α-SMA protein and pSmad2/3 was determined by immunofluorescence microscopy and or Western blotting. The amount of total soluble collagen production was analyzed by the SirCol collagen dye-binding assay.

RESULTS

TGF-beta 1 stimulation increased ROS production by NPDFs. [6]-Gingerol decreased the production of ROS in TGF-beta 1-induced NPDFs. Myofibroblast differentiation, collagen production, and phosphorylation of Smad2/3 were prevented by [6]-gingerol and inhibition of ROS generation with antioxidant such as diphenyliodonium, N-acetylcysteine, and ebselen.

CONCLUSION

These results suggest the possibility that [6]-gingerol may play an important role in inhibiting the production of the ECM in the development of nasal polyps through an antioxidant effect.

摘要

背景

[6]-姜酚是生姜中的主要辛辣成分之一,具有多种作用,包括抗炎和抗氧化作用。活性氧 (ROS) 在成纤维细胞向肌成纤维细胞的表型转化过程中释放,该过程通过诱导细胞外基质 (ECM) 积累参与鼻息肉的生长。本研究旨在确定 [6]-姜酚对鼻息肉衍生成纤维细胞 (NPDF) 的肌成纤维细胞分化和胶原产生的影响,并确定 [6]-姜酚的作用是否与抗氧化作用有关。

方法

NPDF 孵育并与转化生长因子 (TGF) β1 一起处理。使用 2″,7″-二氯荧光素二乙酸酯测定 NPDF 产生的 ROS。通过荧光显微镜捕获荧光,并使用荧光计进行测量。通过逆转录-聚合酶链反应测定α-平滑肌肌动蛋白 (SMA) 和胶原 IV 型 mRNA 的表达,通过免疫荧光显微镜和/或 Western blot 测定α-SMA 蛋白和 pSmad2/3 的表达。通过 SirCol 胶原染色结合测定分析总可溶性胶原产生量。

结果

TGF-β1 刺激增加了 NPDF 中 ROS 的产生。[6]-姜酚减少了 TGF-β1 诱导的 NPDF 中 ROS 的产生。肌成纤维细胞分化、胶原产生和 Smad2/3 的磷酸化被 [6]-姜酚以及抗氧化剂如二苯基碘𬭩、N-乙酰半胱氨酸和 ebselen 抑制 ROS 生成所阻止。

结论

这些结果表明,[6]-姜酚可能通过抗氧化作用在抑制鼻息肉发展过程中 ECM 的产生中发挥重要作用。

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