Development of the novel therapeutic modality for hyperplastic scar and keloid using short chain fatty acids and polyunsaturated fatty acids

我们发现短链脂肪酸和多不饱和脂肪酸的抗纤维化作用，其中丁酸和二十二碳六烯酸的组合效果最好。机制方面，我们发现其对正常人真皮和瘢痕疙瘩成纤维细胞中α - sma、tgf - β 1、I型胶原和III型胶原等促纤维化因子的表达有抑制作用，抑制细胞增殖，促进细胞凋亡。在添加促炎细胞因子或铜绿假单胞菌衍生的LPS或tgf - β 1刺激的病理模型中也发现了这些抗纤维化作用。作为这些作用的关键机制，PGE2的产生，作为抗纤维化的脂质介质和组蛋白乙酰化的丁酸盐被揭示。

We revealed the antifibrogenic effects of short chain fatty acids and polyunsaturated fatty acids, and the best combination is butyrate and docosahexaenoic acid among those fatty acids. As the mechanisms, we found the inhibitory effects on the expressions of profibrotic factors including alpha-SMA, TGF-beta1, type I collagen and type III collagen, and the inhibition of cell proliferation, and promotion of apoptosis in normal human dermal and keloid fibroblasts. These antifibrogenic effects were also found in the pathological models with addition of proinflammatory cytokines or pseudomonas aeruginosa derived LPS or TGF-beta1 stimulation. As the key mechanisms of these effects, the production of PGE2, as an antifibrogenic lipid mediator, and the histone acetylation by butyrate were revealed.