南方医科大学学报

南方医科大学学报 ›› 2021, Vol. 41 ›› Issue (5): 687-693.doi: 10.12122/j.issn.1673-4254.2021.05.08

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莪术醇通过蛋白激酶信号通路抑制瘢痕疙瘩成纤维细胞的增殖和胶原合成

袁巍巍，孙 辉，于 丽，王京波   

  • 出版日期:2021-05-20 发布日期:2021-06-11

Curcumol inhibits keloid fibroblast proliferation and collagen synthesis through the ERK signaling pathway

  • Online:2021-05-20 Published:2021-06-11

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摘要： 目的 研究莪术醇（curcumol）对瘢痕疙瘩成纤维细胞增殖、凋亡和胶原合成的影响及潜在机制。方法 用不同浓度的莪术醇（10、20、40、80、160 mg/L）处理瘢痕疙瘩成纤维细胞（KF）作为不同浓度莪术醇组；用20 μmol/L 蛋白激酶（ERK）信号通路激活剂异丙肾上腺素盐酸盐（ISO）和160 mg/L莪术醇处理KF细胞，记为curcumol 160 mg/L+ISO组，Western blot检测KF细胞中增殖蛋白（Cyclin D1、PCNA）、纤维化标记蛋白（Col1A1、Col3A1、α-SMA）、凋亡蛋白（Bcl-2、Bax、Cleaved caspase-3）、ERK信号通路蛋白（p-ERK1/2、p-MEK、p-c-Raf）表达水平，MTT法和流式细胞术分别检测细胞增殖和凋亡率。结果 不同浓度的莪术醇（10、20、40、80、160 mg/L）均可降低细胞Cyclin D1、PCNA、Bcl-2蛋白含量，抑制纤维化标记蛋白Col1A1、Col3A1、α-SMA蛋白表达，抑制细胞外调节ERK信号通路蛋白p-ERK1/2、p-MEK、p-c-Raf表达，提高Bax、cleaved caspase-3表达量，抑制KF细胞增殖、胶原合成，促进细胞凋亡，抑制ERK信号通路（P<0.05）。ERK信号通路激活剂ISO（20 μmol/L）可逆转莪术醇（160 mg/L）对KF细胞增殖、凋亡、胶原合成和ERK信号通路的作用。结论 莪术醇通过ERK信号通路调控瘢痕疙瘩成纤维细胞增殖、凋亡和胶原合成。

关键词: 瘢痕疙瘩成纤维细胞；增殖；莪术醇；胶原合成；ERK信号通路

Abstract: Objective To assess the effects of curcumol on the proliferation, apoptosis and collagen synthesis of keloid fibroblasts and explore the underlying mechanism. Methods Keloid fibroblasts were treated with different concentrations of curcumol (10, 20, 40, 80 and 160 mg/L) or with 160 mg/L curcumol and 20 μmol/L ISO (an ERK signaling pathway activator). Western blotting was performed to detect the expression levels of proliferation-associated proteins (cyclin D1 and PCNA), fibrosis marker proteins (Col1A1, Col3A1 and α-SMA), apoptosis proteins (Bcl-2, Bax and cleaved caspase-3) and ERK signaling pathway proteins (p-ERK1/2, p-MEK and p-c-Raf) in the cells. MTT assay and flow cytometry were used to evaluate the proliferation and apoptosis rate of the treated cells, respectively. Results Curcumol at 10, 20, 40, 80 and 160 mg/L all reduced the protein expressions of cyclin D1, PCNA and Bcl-2, inhibited the expressions of fibrotic marker proteins Col1A1, Col3A1 and α-SMA, decreased the levels of ERK signaling pathway proteins p-ERK1/2, p-MEK and p-c-Raf, and increased the expressions of Bax and cleaved caspase-3 proteins (P<0.05). Curcumol treatment at 160 mg/L obviously inhibited the proliferation and collagen synthesis, promoted cell apoptosis and inhibited the ERK signaling pathway in the keloid fibroblasts; treatment with ISO significantly reversed the effects of curcumol on the proliferation, apoptosis, collagen synthesis and ERK signal pathway of the cells. Conclusions Curcumol regulates proliferation, apoptosis and collagen synthesis in keloid fibroblasts through the ERK signaling pathway.

Key words: keloid fibroblasts; proliferation; curcumol; collagen synthesis; ERK signaling pathway