Control of the intracellular levels of prostaglandin E2 through inhibition of the 15-hydroxyprostaglandin dehydrogenase for wound healing
Control of the intracellular levels of prostaglandin E2 through inhibition of the 15-hydroxyprostaglandin dehydrogenase for wound healing
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DOI：
10.1016/j.bmc.2013.05.049
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发表时间：
2013-08-01
影响因子：
3.5
通讯作者：
Cho, Hoon
中科院分区：
文献类型：
--
作者：
Choi, Dubok;Piao, Yu Lan;Cho, Hoon
过度的瘢痕形成是伤口愈合的异常形式，并且是伤口愈合期间成纤维细胞的过度功能和细胞外基质的过度积累的指示。许多实验数据表明，前列腺素E-2（PGE（2））在预防过度瘢痕形成中起作用。然而，它在血液中的半衰期很短，其氧化为15-酮基前列腺素是由15-羟基前列腺素脱氢酶（15-PGDH）催化的。以前，我们报道了15-PGDH抑制剂显著增加A549细胞中PGE（2）水平。在我们继续尝试开发高效15-PGDH抑制剂的过程中，我们新合成了各种噻唑烷-2，4-二酮衍生物。化合物27、28、29和30的IC 50值分别为0.048、0.020、0.038和0.048 μ M。它们还增加A549细胞中PGE（2）的水平。特别是，化合物28显著增加PGE（2）的水平（260 pg/mL），其比对照高约5倍。在HaCaT细胞的汇合单层中分析划痕伤口。相对于对照，暴露于化合物28的细胞显示出显著改善的伤口愈合。(C)2013作者由爱思唯尔有限公司出版。保留所有权利。
Excessive scar formation is an aberrant form of wound healing and is an indication of an exaggerated function of fibroblasts and excess accumulation of extracellular matrix during wound healing. Much experimental data suggests that prostaglandin E-2 (PGE(2)) plays a role in the prevention of excessive scarring. However, it has a very short half-live in blood, its oxidization to 15-ketoprostaglandins is catalyzed by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Previously, we reported that 15-PGDH inhibitors significantly increased PGE(2) levels in A549 cells. In our continuing attempts to develop highly potent 15-PGDH inhibitors, we newly synthesized various thiazolidine-2,4-dione derivatives. Compound 27, 28, 29, and 30 demonstrated IC50 values of 0.048, 0.020, 0.038 and 0.048 mu M, respectively. They also increased levels of PGE(2) in A549 cells. Especially, compound 28 significantly increased level of PGE(2) at 260 pg/mL, which was approximately fivefold higher than that of control. Scratch wounds were analyzed in confluent monolayers of HaCaT cells. Cells exposed to compound 28 showed significantly improved wound healing with respect to control. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.