Calcimycin Suppresses S100A4 Expression and Inhibits the Stimulatory Effect of Transforming Growth Factor beta1 on Keloid Fibroblasts.
Calcimycin Suppresses S100A4 Expression and Inhibits the Stimulatory Effect of Transforming Growth Factor beta1 on Keloid Fibroblasts.
复制标题
钙霉素抑制 S100A4 表达并抑制转化生长因子 1 对瘢痕疙瘩成纤维细胞的刺激作用
DOI：
10.1097/sap.0000000000001502
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发表时间：
2018
影响因子：
1.5
通讯作者：
Li Qing-Feng
中科院分区：
文献类型：
--
作者：
Zhao Yi-Xuan;Ho Chia-Kang;Xie Yun;Chen Ya-Hong;Li Hai-Zhou;Zhang Guo-You;Li Qing-Feng
最近的研究表明，S100A4参与组织纤维化，而钙霉素作为一种新的S100A4转录抑制剂抑制这一过程。然而，在瘢痕疙瘩成纤维细胞（KFs）中，钙霉素和S100A4之间的关系和机制尚不清楚。本研究旨在探讨钙霉素对KFs中S100A4表达及发病机制的影响。培养瘢痕疙瘩成纤维细胞，并将其暴露于不同浓度的钙霉素中，无论是否存在转化生长因子β1 （TGF-β1）。结果表明，瘢痕疙瘩源性成纤维细胞中S100A4的表达明显高于正常皮肤成纤维细胞。钙霉素以浓度和时间依赖的方式抑制S100A4。此外，钙霉素抑制TGF-β1诱导的I型胶原、纤维连接蛋白和α-平滑肌肌动蛋白的表达和细胞活力。此外，钙霉素调节TGF-β/Smad靶基因Smad7的表达和TGF-β1诱导的Smad2/3的磷酸化。本研究首次证实了KFs中存在S100A4。钙霉素抑制S100A4的表达，抑制KF的增殖、迁移和细胞外基质（ECM）的合成。综上所述，这些结果表明钙霉素可能是治疗瘢痕疙瘩或其他相关纤维化疾病的候选药物。
Recent researches have indicated that S100A4 participates in tissue fibrosis, whereas calcimycin inhibits this process as a novel S100A4 transcription inhibitor. However, the relationship and mechanisms between calcimycin and S100A4 in keloid fibroblasts (KFs) remain unknown. The present research was aimed to evaluate the effect of calcimycin on S100A4 expression and pathogenesis in KFs. Keloid fibroblasts were cultured and exposed to different concentrations of calcimycin in the absence or presence of transforming growth factor β1 (TGF-β1). The results showed that the expression of S100A4 was significantly increased in keloid derived fibroblasts compared with normal skin fibroblasts. Calcimycin depressed S100A4 in a concentration-and time-dependent manner. Moreover, calcimycin suppressed TGF-β1–induced collagen type I, fibronectin, and α-smooth muscle actin expression and cell viability in cultured KFs. Furthermore, calcimycin modulated expression of TGF-β/Smad target genes Smad7 and phosphorylation of TGF-β1–induced Smad2/3. This research for the first time confirmed the presence of S100A4 in KFs. Calcimycin inhibits the expression of S100A4, as well as KF proliferation and migration and extracellular matrix (ECM) synthesis. Taken together, these results indicate that calcimycin might be a therapeutic candidate to keloid or other related fibrotic disorders.