他莫昔芬抑制TGF-β/Smad通路减轻人皮肤成纤维细胞病理性增生

doi:10.16352/j.issn.1001-6325.2022.09.1367

基础医学与临床 ›› 2022, Vol. 42 ›› Issue (9): 1367-1373.doi: 10.16352/j.issn.1001-6325.2022.09.1367

他莫昔芬抑制TGF-β/Smad通路减轻人皮肤成纤维细胞病理性增生

史春田, 毛姝然, 彭译萱, 肖志波^*

哈尔滨医科大学附属第二医院整形外科, 黑龙江哈尔滨 150086

收稿日期:2021-08-26 修回日期:2021-12-31 出版日期:2022-09-05 发布日期:2022-09-02
通讯作者: xiaozhibodoctor126.com
基金资助:
黑龙江省杰出青年科学基金(JC2017019)

Tamoxifen inhibits TGF-β/Smad pathway and reduces pathological proliferation of human dermal fibroblasts

SHI Chun-tian, MAO Shu-ran, PENG Yi-xuan, XIAO Zhi-bo^*

Department of Plastic Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China

Received:2021-08-26 Revised:2021-12-31 Online:2022-09-05 Published:2022-09-02

摘要/Abstract

摘要： 目的探讨雌激素受体调节剂他莫昔芬在增生性瘢痕发病中的作用及机制。方法提取原代人成纤维细胞培养至4代,并分为3组:对照组、TGF-β1组和TGF-β1＋他莫昔芬组。应用实时定量聚合酶链反应(RT-qPCR)、细胞增殖检测(MTS)、细胞划痕试验、免疫印迹和免疫荧光实验,检测他莫昔芬对转化生长因子诱导的人皮肤成纤维细胞的纤维化因子产生、细胞增殖、迁移和分化能力。结果他莫昔芬(10 μmol/L)抑制人成纤维细胞中的TGF-β1诱导胶原蛋白1、胶原蛋白3、α-SMA等的生成,MTS结果显示,TGF-β1组细胞的增殖活力高于他莫昔芬处理组(P＜0.05),划痕实验表明他莫昔芬干预后细胞的迁移能力减弱,他莫昔芬缓解了人皮肤成纤维细胞分泌胶原及向肌成纤维细胞分化进程。结论本研究证实了他莫昔芬可以抑制人成纤维细胞的病理性增生,可能为增生性瘢痕治疗提供一种新的策略。

关键词: 增生性瘢痕, 他莫昔芬, TGF-β, 皮肤成纤维细胞

Abstract: Objective To explore the function and mechanism of tamoxifen, an estrogen receptor modulator, in the pathogenesis of hyperplatic scar. Methods Primary human fibroblasts were isolated and cultured for 4 generations and then aliquated into 3 groups: control group, TGF-β1 group and TGF-β1+ tamoxifen group. The effects of tamoxifen on human fibrogenic factor production, cell proliferation, migration and differentiation of TGF-β1-induced skin fibroblasts were detected by real-time quantitative polymerase chain reaction (RT-qPCR), MTS, cell scratch test, Western blot and immunofluorescence assay. Results Tamoxifen (10 μmol/L) inhibited the production of collagen 1, collagen 3 and α-SMA induced by TGF-β1 in fibroblasts. MTS results showed that the proliferation activity of TGF-β1 group was higher than that of tamoxifen group (P＜0.05). Wound healing test verified that the migration ability of cells was reduced by tamoxifen intervention. Tamoxifen inhibited collagen secretion and differentiation of skin fibroblasts into muscle fibroblasts. Conclusions The estrogen receptor modulator tamoxifen inhibits pathological proliferation of fibroblasts, so it may be a potential novel strategy for the treatment of hyperplastic scar.

Key words: hyperplastic scar, tamoxifen, TGF-β, skin fibroblasts

中图分类号:

史春田, 毛姝然, 彭译萱, 肖志波. 他莫昔芬抑制TGF-β/Smad通路减轻人皮肤成纤维细胞病理性增生[J]. 基础医学与临床, 2022, 42(9): 1367-1373.

SHI Chun-tian, MAO Shu-ran, PENG Yi-xuan, XIAO Zhi-bo. Tamoxifen inhibits TGF-β/Smad pathway and reduces pathological proliferation of human dermal fibroblasts[J]. Basic & Clinical Medicine, 2022, 42(9): 1367-1373.

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他莫昔芬抑制TGF-β/Smad通路减轻人皮肤成纤维细胞病理性增生

Tamoxifen inhibits TGF-β/Smad pathway and reduces pathological proliferation of human dermal fibroblasts

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