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地塞米松对啮齿动物良性胆管狭窄成纤维细胞中转化生长因子-β1/Smads信号通路表达的影响

Dexamethasone Effect on the Expression of Transforming Growth Factor-β1/Smads Signaling Pathway in Benign Biliary Stricture Fibroblasts in Rodent.

作者信息

Li Ke -Yue, Shi Cheng -Xian, Huang Jian -Zhao, Tang Ke -Li

机构信息

Department of Hepatobiliary Surgery, Guizhou Provincial People's Hospital, Guizhou Province, China.

出版信息

J Coll Physicians Surg Pak. 2017 Mar;27(3):131-134.

PMID:28406769
Abstract

OBJECTIVE

To investigate the effects of dexamethasone on transforming growth factor (TGF)-β1/Smads signaling pathway in benign biliary stricture (BBS) fibroblasts.

STUDY DESIGN

An experimental study.

PLACE AND DURATION OF STUDY

Guizhou Medical University, Guiyang, Guizhou, China, from January to August 2016.

METHODOLOGY

Fibroblasts derived from rabbit BBS model were cultured and identified, then treated by different concentration of dexamethasone (0.02, 0.1 and 0.5 mg/ml). Dexamethasone-treated cells and non-treated control groups were incubated respectively for 48 hours. Cell proliferation was assessed using cell counting kit-8. Relative mRNA expression of TGF-β1, Smad4 and Smad7 were assessed by quantitative RT-PCR. Protein expression of TGF-β1 and Smad4 were investigated by Western blotting.

RESULTS

Treatment with dexamethasone significantly inhibited the proliferation of BBS fibroblasts, significantly attenuated both the mRNA and protein expression of TGF-β1 and Smad4, and significantly up-regulated the mRNA expression of Smad7 in BBS fibroblasts (all p<0.05, 0.1-0.5 mg/ml), and exhibited in a dose-dependent manner.

CONCLUSION

TGF-β1/Smads signaling pathway may play an important role in BBS progression; dexamethasone significantly altered the expression of TGF-β1/Smads signaling pathway and significantly inhibited cell proliferation in rabbit BBS fibroblasts. Therefore, dexamethasone may be a therapeutic option for the prevention of BBS.

摘要

目的

探讨地塞米松对良性胆管狭窄(BBS)成纤维细胞中转化生长因子(TGF)-β1/Smads信号通路的影响。

研究设计

实验研究。

研究地点及时间

2016年1月至8月,中国贵州省贵阳市贵州医科大学。

方法

培养并鉴定源自兔BBS模型的成纤维细胞,然后用不同浓度的地塞米松(0.02、0.1和0.5mg/ml)进行处理。地塞米松处理的细胞和未处理的对照组分别孵育48小时。使用细胞计数试剂盒-8评估细胞增殖。通过定量RT-PCR评估TGF-β1、Smad4和Smad7的相对mRNA表达。通过蛋白质印迹法研究TGF-β1和Smad4的蛋白表达。

结果

地塞米松处理显著抑制了BBS成纤维细胞的增殖,显著减弱了TGF-β1和Smad4的mRNA及蛋白表达,并显著上调了BBS成纤维细胞中Smad7的mRNA表达(所有p<0.05,0.1 - 0.5mg/ml),且呈剂量依赖性。

结论

TGF-β1/Smads信号通路可能在BBS进展中起重要作用;地塞米松显著改变了TGF-β1/Smads信号通路的表达,并显著抑制了兔BBS成纤维细胞的增殖。因此,地塞米松可能是预防BBS的一种治疗选择。

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