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

我们揭示了短链脂肪酸和多不饱和脂肪酸的抗纤维化作用，其中最好的组合是丁酸和二十二碳六烯酸。其作用机制为抑制促纤维化因子α-SMA、TGF-β 1、I型胶原和III型胶原的表达，抑制正常人皮肤和瘢痕疙瘩成纤维细胞增殖，促进细胞凋亡。在加入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，作为抗纤维化脂质介质的PGE 2的产生以及丁酸酯对组蛋白的乙酰化被揭示。

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.