Department of Plastic Surgery, Tongde Hospital of Zhejiang Province, Hangzhou, China.
Adv Clin Exp Med. 2021 Mar;30(3):263-271. doi: 10.17219/acem/131753.
microRNAs are involved in a variety of physiological and pathophysiological processes, but their role in the pathogenesis of hypertrophic scars (HS) is not fully understood. Transforming growth factor β1 (TGF-β1) plays an important role in the genesis and development of HS.
In this study, we hypothesized that a post-translational miRNA mechanism regulates the expression of TGF-β1 in HS fibroblasts (HSFBs) and participates in the development of HS.
Predictions from EBCORI, PicTar and miRBase databases showed that miR-124-3p can target and regulate the expression of TGF-β1. We collected HS tissue and corresponding normal tissue from 25 patients with HS who had been operated on for the first time.
The expression level of miR-124-3p in HS tissue was significantly lower than in normal tissue, while the expression level of TGF-β1 mRNA was significantly higher than in normal tissue (p < 0.05), showing a negative correlation between them. Results from a luciferase reporter assay showed that miR-124-3p targets the 3'-UTR of TGF-β1 and inhibits its expression. After miR-124-3p mimics were transfected into HSFBs, the expression of TGF-β1, α-smooth muscle actin (α-SMA), collagen I, survivin, and Bcl-2 were reduced and the expression of Bax was increased, with significant decreases in DNA synthesis, proliferation and survival. However, after a miR-124-3p inhibitor was transfected into HSFBs, these effects were reversed as the expression of TGF-β1, α-SMA, collagen I, survivin, and Bcl-2 increased, expression of Bax decreased, and DNA synthesis, proliferation and survival cells increased significantly.
miR-124-3p can inhibit the proliferation of HSFBs by targeting TGF-β1, and miR-124-3p may thus be a potential therapeutic target in HS.
microRNAs 参与多种生理和病理生理过程，但它们在肥厚性瘢痕（HS）发病机制中的作用尚不完全清楚。转化生长因子β1（TGF-β1）在 HS 的发生和发展中起重要作用。
本研究假设一种翻译后 miRNA 机制调节 HS 成纤维细胞（HSFBs）中 TGF-β1 的表达，并参与 HS 的发展。
EBCORI、PicTar 和 miRBase 数据库的预测表明，miR-124-3p 可以靶向并调节 TGF-β1 的表达。我们收集了 25 例首次手术治疗的 HS 患者的 HS 组织和相应的正常组织。
HS 组织中 miR-124-3p 的表达水平明显低于正常组织，而 TGF-β1 mRNA 的表达水平明显高于正常组织（p<0.05），呈负相关。荧光素酶报告基因检测结果显示，miR-124-3p 靶向 TGF-β1 的 3'-UTR 并抑制其表达。转染 miR-124-3p 模拟物后，HSFBs 中 TGF-β1、α-平滑肌肌动蛋白（α-SMA）、胶原 I、存活素和 Bcl-2 的表达减少，Bax 的表达增加，DNA 合成、增殖和存活减少。然而，转染 miR-124-3p 抑制剂后，TGF-β1、α-SMA、胶原 I、存活素和 Bcl-2 的表达增加，Bax 的表达减少，DNA 合成、增殖和存活细胞显著增加，这些作用被逆转。
miR-124-3p 通过靶向 TGF-β1 抑制 HSFBs 的增殖，因此 miR-124-3p 可能是 HS 的潜在治疗靶点。
