Seo Seung Yong, Han Song-Iy, Bae Chun Sik, Cho Hoon, Lim Sung Chul
Department of Pathology, Chosun University School of Medicine, Gwangju, Republic of Korea.
Division of Natural Medical Sciences, College of Health Science, Chosun University, Gwangju, Republic of Korea.
Prostaglandins Leukot Essent Fatty Acids. 2015 Jun;97:35-41. doi: 10.1016/j.plefa.2015.03.005. Epub 2015 Apr 7.
PGE2 is an important mediator of wound healing. It is degraded and inactivated by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Various growth factors, type IV collagen, TIMP-2 and PGE2 are important mediators of inflammation involving wound healing. Overproduction of TGF-β and suppression of PGE2 are found in excessive wound scarring. If we make the condition downregulating growth factors and upregulating PGE2, the wound will have a positive effect which results in little scar formation after healing. TD88 is a 15-PGDH inhibitor based on thiazolinedione structure. We evaluated the effect of TD88 on wound healing. In 10 guinea pigs (4 control and 6 experimental groups), we made four 1cm diameter-sized circular skin defects on each back. TD88 and vehicle were applicated on the wound twice a day for 4 days in the experimental and control groups, respectively. Tissue samples were harvested for qPCR and histomorphometric analyses on the 2nd and 4th day after treatment. Histomorphometric analysis showed significant reepithelization in the experimental group. qPCR analysis showed significant decrease of PDGF, CTGF and TIMP-2, but significant increase of type IV collagen in the experimental group. Taken together TD88 could be a good effector on wound healing, especially in the aspects of prevention of scarring.
前列腺素E2（PGE2）是伤口愈合的重要介质。它会被15-羟基前列腺素脱氢酶（15-PGDH）降解并失活。多种生长因子、IV型胶原蛋白、金属蛋白酶组织抑制剂-2（TIMP-2）和PGE2是涉及伤口愈合的炎症的重要介质。在过度的伤口瘢痕形成中发现转化生长因子-β（TGF-β）过度产生和PGE2受到抑制。如果我们使生长因子下调而PGE2上调，伤口将产生积极效果，愈合后瘢痕形成很少。TD88是一种基于噻唑啉二酮结构的15-PGDH抑制剂。我们评估了TD88对伤口愈合的影响。在10只豚鼠（4只对照组和6只实验组）中，我们在每只豚鼠背部制造了4个直径为1厘米的圆形皮肤缺损。实验组和对照组分别每天在伤口上涂抹TD88和赋形剂两次，持续4天。在治疗后的第2天和第4天采集组织样本进行定量聚合酶链反应（qPCR）和组织形态计量学分析。组织形态计量学分析显示实验组有明显的上皮再形成。qPCR分析显示实验组中血小板衍生生长因子（PDGF）、结缔组织生长因子（CTGF）和TIMP-2显著减少，但IV型胶原蛋白显著增加。综上所述，TD88可能是伤口愈合的良好效应物，尤其是在预防瘢痕形成方面。
