Laboratory of Cell Biology, Federal University of Alagoas, 57072-900, Maceió, Brazil.
NuMeCan Institute (Nutrition, Metabolism and Cancer), Université de Rennes, INSERM, INRA, F-35000, Rennes, France.
J Tissue Viability. 2021 Aug;30(3):363-371. doi: 10.1016/j.jtv.2021.05.003. Epub 2021 May 24.
Hydroxycinnamic acids their derivatives have various pharmacological properties. The hydroxycinnamic acid derivatives, methyl cinnamate, trans-cinnamic, and p-coumaric acids have been the object of study in the treatment of skin wounds. However, it is unclear whether these derivatives exert a direct beneficial effect on fibroblast function. In this study, we evaluated the effects of methyl cinnamate, trans-cinnamic, and p-coumaric acids on fibroblast migration in vitro.
NIH 3T3 and L929 fibroblast cell lines were exposed to each drug at several concentrations and the effect on cell viability, cell cycle, and extracellular matrix production were assessed by MTT assay, flow cytometry, and immunofluorescence staining, respectively. The effect on cell migration was examined using scratch assay.
The results showed that hydroxycinnamic acid derivatives not affect cell viability, but increase fibroblast migration in the in vitro scratch-wound healing assay. They also induced an increase in S and G2/M phases accompanied by a decrease in the G0/G1 phase of the cell cycle. The cell proliferation inhibitor mitomycin C abolished the effect induced by p-coumaric acid and methyl cinnamate, indicating that only the trans-cinnamic acid stimulated migration. A transwell migration assay confirmed that trans-cinnamic acid-treated fibroblasts exhibited increased migration compared with untreated cells. trans-Cinnamic acid-induced fibroblast migration was decreased by PKA inhibitor and p38-MAPK inhibitor but not by JNK inhibitor. Additionally, trans-cinnamic acid-treated fibroblasts showed an increase in the production of laminin and collagen type I.
Our study showed that trans-cinnamic acid improves fibroblast migration and modulates extracellular matrix synthesis, indicating its potential for accelerating the healing process.
羟基肉桂酸及其衍生物具有多种药理学特性。羟基肉桂酸衍生物，肉桂酸甲酯、反式肉桂酸和对香豆酸，一直是治疗皮肤创伤的研究对象。然而，这些衍生物是否对成纤维细胞功能有直接的有益作用尚不清楚。在这项研究中，我们评估了肉桂酸甲酯、反式肉桂酸和对香豆酸对成纤维细胞体外迁移的影响。
NIH 3T3 和 L929 成纤维细胞系分别暴露于几种浓度的每种药物，通过 MTT 测定法、流式细胞术和免疫荧光染色分别评估对细胞活力、细胞周期和细胞外基质产生的影响。通过划痕试验评估对细胞迁移的影响。
结果表明，羟基肉桂酸衍生物不影响细胞活力，但增加了体外划痕愈合试验中成纤维细胞的迁移。它们还诱导 S 和 G2/M 期增加，同时细胞周期的 G0/G1 期减少。细胞增殖抑制剂丝裂霉素 C 消除了对香豆酸和肉桂酸甲酯诱导的作用，表明只有反式肉桂酸刺激迁移。Transwell 迁移试验证实，与未处理的细胞相比，用反式肉桂酸处理的成纤维细胞表现出迁移增加。PKA 抑制剂和 p38-MAPK 抑制剂而非 JNK 抑制剂可降低反式肉桂酸诱导的成纤维细胞迁移。此外，用反式肉桂酸处理的成纤维细胞表现出层粘连蛋白和 I 型胶原合成增加。
我们的研究表明，反式肉桂酸可改善成纤维细胞迁移并调节细胞外基质合成，表明其在加速愈合过程中具有潜力。
