Koga Yuka, Maeshige Noriaki, Tabuchi Hiroto, Uemura Mikiko, Aoyama-Ishikawa Michiko, Miyoshi Makoto, Katakami Chikako, Usami Makoto
Division of Nutrition and Metabolism, Department of Biophysics, Kobe University Graduate School of Health Sciences, Tomogaoka 7-10-2, Suma-ku, Kobe, Japan.
Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences, Tomogaoka 7-10-2, Suma-ku, Kobe, Japan.
Int J Ophthalmol. 2017 Sep 18;10(9):1337-1343. doi: 10.18240/ijo.2017.09.01. eCollection 2017.
To evaluate the antifibrogenic effects of butyrate or phenylbutyrate, a chemical derivative of butyrate, in human pterygium fibroblasts.
Human pterygium fibroblasts obtained from patient pterygium tissue were treated with butyrate or phenylbutyrate for 48h. Expression of α-smooth muscle actin, collagen I, collagen III and matrix metalloproteinase-1 mRNA was measured by quantitative real-time reverse transcription polymerase chain reaction, and acetylated histone was evaluated by Western blotting.
Butyrate inhibited α-smooth muscle actin, type III collagen and matrix metalloproteinase-1 expressions, and phenylbutyrate inhibited types I and III collagen and matrix metalloproteinase-1 expressions without changing cell viability as well as both of these increased histone acetylation. These results suggested that butyrate and phenylbutyrate suppress fibrosis through a mechanism involving histone deacetylase inhibitor.
This indicates that butyrate or phenylbutyrate have antifibrogenic effects in human pterygium fibroblasts and could be novel types of prophylactic and/or therapeutic drugs for pterygium, especially phenylbutyrate, which does not have the unpleasant smell associated with butyrate.
评估丁酸盐或其化学衍生物苯丁酸盐对人翼状胬肉成纤维细胞的抗纤维化作用。
用丁酸盐或苯丁酸盐处理从患者翼状胬肉组织获取的人翼状胬肉成纤维细胞48小时。通过定量实时逆转录聚合酶链反应测量α-平滑肌肌动蛋白、I型胶原、III型胶原和基质金属蛋白酶-1 mRNA的表达,并通过蛋白质免疫印迹法评估乙酰化组蛋白。
丁酸盐抑制α-平滑肌肌动蛋白、III型胶原和基质金属蛋白酶-1的表达,苯丁酸盐抑制I型和III型胶原以及基质金属蛋白酶-1的表达,且不改变细胞活力,二者均增加组蛋白乙酰化。这些结果表明,丁酸盐和苯丁酸盐通过涉及组蛋白去乙酰化酶抑制剂的机制抑制纤维化。
这表明丁酸盐或苯丁酸盐对人翼状胬肉成纤维细胞具有抗纤维化作用,可能是翼状胬肉新型的预防和/或治疗药物,尤其是苯丁酸盐,它没有与丁酸盐相关的难闻气味。