Torii Kazuhiro, Maeshige Noriaki, Aoyama-Ishikawa Michiko, Miyoshi Makoto, Terashi Hiroto, Usami Makoto
Division of Nutrition and Metabolism, Department of Biophysics, Graduate School of Health Sciences, Kobe University - Kobe, Japan.
Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University - Kobe, Japan.
An Bras Dermatol. 2017 Mar-Apr;92(2):184-190. doi: 10.1590/abd1806-4841.20176198.
: A single, effective therapeutic regimen for keloids has not been established yet, and the development of novel therapeutic approaches is expected. Butyrate, a short-chain fatty acid, and docosahexaenoic acid (DHA), a ω-3 polyunsaturated fatty acid, play multiple anti-inflammatory and anticancer roles via their respective mechanisms of action.
: In this study, we evaluated the antifibrogenic effects of their single and combined use on keloid fibroblasts.
: Keloid fibroblasts were treated with butyrate (0-16 mM) and/or DHA (0-100 µM) for 48 or 96 h.
: Butyrate inhibited cell proliferation, and α-smooth muscle actin (α-SMA) and type III collagen expressions, with inhibition of the transforming growth factor (TGF)-β1 and TGF-β type I receptor expressions and increased prostaglandin E2 with upregulation of cyclooxygenase-1 expression with induction of histone acetylation. DHA inhibited α-SMA, type III collagen, and TGF-β type I receptor expressions. Then, the butyrate/DHA combination augmented the antifibrogenic effects, resulting in additional inhibition of α-SMA, type I and III collagen expressions, with strong disruption of stress fiber and apoptosis induction. Moreover, the butyrate/DHA combination inhibited the cyclooxygenase-2 expression, suggesting stronger anti-inflammatory effect than each monotherapy.
: Activation in keloid tissue is affected not only by fibroblasts but also by epithelial cells and immune cells. Evaluation of the effects by butyrate and DHA in these cells or in an in vivo study is required.
: This study demonstrated that butyrate and docosahexaenoic acid have antifibrogenic effects on keloid fibroblasts and that these may exert therapeutic effects for keloid.
尚未建立针对瘢痕疙瘩的单一有效治疗方案，因此期待开发新的治疗方法。丁酸盐（一种短链脂肪酸）和二十二碳六烯酸（DHA，一种ω-3多不饱和脂肪酸）通过各自的作用机制发挥多种抗炎和抗癌作用。
在本研究中，我们评估了它们单独使用和联合使用对瘢痕疙瘩成纤维细胞的抗纤维化作用。
用丁酸盐（0 - 16 mM）和/或DHA（0 - 100 µM）处理瘢痕疙瘩成纤维细胞48或96小时。
丁酸盐抑制细胞增殖、α平滑肌肌动蛋白（α-SMA）和III型胶原蛋白表达，抑制转化生长因子（TGF）-β1和TGF-β I型受体表达，并通过诱导组蛋白乙酰化上调环氧合酶-1表达来增加前列腺素E2。DHA抑制α-SMA、III型胶原蛋白和TGF-β I型受体表达。然后，丁酸盐/DHA组合增强了抗纤维化作用，导致对α-SMA、I型和III型胶原蛋白表达的进一步抑制，强烈破坏应力纤维并诱导细胞凋亡。此外，丁酸盐/DHA组合抑制环氧合酶-2表达，表明其抗炎作用比每种单一疗法更强。
瘢痕疙瘩组织中的激活不仅受成纤维细胞影响，还受上皮细胞和免疫细胞影响。需要评估丁酸盐和DHA对这些细胞的作用或进行体内研究。
本研究表明丁酸盐和二十二碳六烯酸对瘢痕疙瘩成纤维细胞具有抗纤维化作用，这些作用可能对瘢痕疙瘩发挥治疗效果。
