转化生长因子-β（TGF-β）介导BRD4/信号转导子和转录激活子3（STAT3）信号通路以促进成纤维细胞增殖从而促进瘢痕疙瘩进展的机制。

The mechanism of TGF-β mediating BRD4/STAT3 signaling pathway to promote fibroblast proliferation and thus promote keloid progression.

作者信息

Bai Ruiqi, Hao Lixia, Zhou Guiwen, Fu Qiang, Zhang Peixuan, Lin Pianpian, Chen Minliang

机构信息

Department of Plastic and Reconstructive Surgery, Senior Department of Burns and Plastic Surgery, The Forth Medical Center of Chinese PLA General Hospital, Beijing, 100142, China.

出版信息

Heliyon. 2024 Sep 21;10(19):e38188. doi: 10.1016/j.heliyon.2024.e38188. eCollection 2024 Oct 15.

UNLABELLED

The purpose of this study was to investigate the effect of TGF-β on keloid and its molecular mechanism in fibroblasts.

METHODS

The difference between normal tissue and keloid tissue can be detected using HE staining. Fibroblasts were treated with TGF-β, and then treated with the BRD4 inhibitor JQ1 and the STAT3 activator Colivelin TFA. Western blot was used to measure the relative protein expression of TGF-β, BRD4, p-STAT3, p-EZH2, C-myc, KLF2, KLF4, α-SMA, and Collagen-I. Immunofluorescence staining was used to measure the relative fluorescence intensity of BRD4, p-STAT3, α-SMA, and Collagen-I. Cell proliferation ability was evaluated by CCK-8 assay and colony formation assay.

RESULTS

The expression of TGF-β and BRD4 was significantly higher in keloid tissue compared to normal tissue. TGF-β mediated the BRD4/STAT3 signaling pathway to inhibit p-EZH2 and promote the expression of C-myc, KLF2, KLF4, α-SMA, and Collagen-I. Additionally, TGF-β mediated the BRD4/STAT3 signaling pathway to enhance fibroblast proliferation.

CONCLUSION

TGF-β mediates the BRD4/STAT3 signaling pathway to promote fibroblast proliferation and contribute to the progression of keloid.

未标记

本研究的目的是探讨转化生长因子-β（TGF-β）对瘢痕疙瘩的影响及其在成纤维细胞中的分子机制。

方法

采用苏木精-伊红（HE）染色检测正常组织与瘢痕疙瘩组织之间的差异。用TGF-β处理成纤维细胞，然后用BRD4抑制剂JQ1和信号转导及转录激活蛋白3（STAT3）激活剂Colivelin TFA处理。采用蛋白质免疫印迹法检测TGF-β、BRD4、磷酸化STAT3（p-STAT3）、磷酸化EZH2（p-EZH2）、原癌基因C-myc、 Kruppel样因子2（KLF2）、Kruppel样因子4（KLF4）、α-平滑肌肌动蛋白（α-SMA）和I型胶原蛋白（Collagen-I）的相对蛋白表达。采用免疫荧光染色法检测BRD4、p-STAT3、α-SMA和Collagen-I的相对荧光强度。通过细胞计数试剂盒-8（CCK-8）法和集落形成试验评估细胞增殖能力。