Prostaglandin E2 불활성화 효소인 15-hydroxyprostaglandin dehydrogenase 억제제의 창상치유효과

Abstract

Prostaglandin E2 (PGE2) is known as an important mediator of various types of wound healing. It is degraded and inactivated by NAD+-dependent 15-hydroxyprostagaladin dehydrogenase (15-PGDH). Thus, inhibitors of 15-PGDH will be valuable for the treatment of diseases requiring elevated PGE2. The inflammatory process has direct effects on wound healing. Hypertrophic 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. Various growth factors including TGF-β, PDGF-D, VEGF, and CTGF, type IV collagen. TIMP-2 and PG E2 are important mediators of inflammation involving wound healing. Overproduction of TGF-β and suppression of PGE2 are found in excessive wound scarring compared with normal wound healing. 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 wound healing. 5-(2-chloro-3-(3-phenylpropoxy) benzylidene) thiazolidine-2,4-dione (TD88) is a newly synthesized 15-PGDH inhibitor based on thiazolinedione structure. We evaluated the effect of TD88 on wound healing. In 10 guinea pigs (4 control group and 6 experimental group), we made four 1 cm 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 quantitative PCR (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 growth factors (PDGF and 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 downregulating growth factors and upregulating PGE2 and thereby might play a role in the prevention of excessive scarring. The hypertrophic scar/keloid treatment algorithms that are currently available are likely to be significantly improved in the future by high-quality clinical trials.