Bioscience Research Institute, AmorePacific Corporation R&D Center, 314-1 Bora-dong, Giheung-gu, Yongin, Kyeonggi-do, Korea.
Dermatology. 2012;224(4):352-60. doi: 10.1159/000339337. Epub 2012 Jun 29.
Cathepsin G, a serine protease that is activated by ultraviolet (UV) radiation, increases matrix metalloproteinase-1 (MMP-1) expression in fibroblasts through fibronectin (Fn) fragmentation and promotes the conversion of proMMP-1 to active MMP-1.
This study investigated whether [2-[3-[[(1-benzoyl-4-piperidinyl)methylamino]carbonyl]-2-naphthalenyl]-1-(1-naphthalenyl)-2-oxoethyl]-phosphonic acid (KPA), a cathepsin G inhibitor, plays any role in extracellular matrix (ECM) damage in an in vitro 3D dermal equivalent (DE) and an in vivo ultraviolet B (UVB)-irradiated hairless mice.
We examined the potential ECM-protective effects of a cathepsin G inhibitor in an in vitro 3D DE model and an in vivo UVB-irradiated hairless mouse skin model.
Among five known serine protease inhibitors, KPA showed the strongest potency and selectivity against cathepsin G. KPA inhibited the cathepsin G-mediated MMP-1 increase and alleviated the downregulation of mRNAs encoding collagen and tissue inhibitor of matrix metalloproteinase-1 in an in vitro 3D DE model. Most importantly, topical application of KPA (0.025%) to the dorsal skin of hairless mice enhanced collagen expression and attenuated UVB-induced Fn fragmentation and upregulation of MMP-2 and MMP-9 activities.
Cathepsin G inhibitors may be useful for the prevention of UVB-induced photoaging through amelioration of ECM damage and MMP upregulation.
组织蛋白酶 G 是一种丝氨酸蛋白酶，可被紫外线（UV）辐射激活，通过纤维连接蛋白（Fn）片段化增加成纤维细胞中基质金属蛋白酶-1（MMP-1）的表达，并促进 proMMP-1 向活性 MMP-1 的转化。
本研究探讨了组织蛋白酶 G 抑制剂[2-[3-[[（1-苯甲酰基-4-哌啶基）甲基氨基]羰基]-2-萘基]-1-（1-萘基）-2-氧代乙基]-膦酸（KPA）]在体外 3D 真皮等效物（DE）和体内 UVB 照射无毛小鼠中是否对细胞外基质（ECM）损伤起作用。
我们在体外 3D DE 模型和体内 UVB 照射无毛小鼠皮肤模型中检查了组织蛋白酶 G 抑制剂的潜在 ECM 保护作用。
在五种已知的丝氨酸蛋白酶抑制剂中，KPA 对组织蛋白酶 G 的活性最强且选择性最高。KPA 抑制组织蛋白酶 G 介导的 MMP-1 增加，并减轻了体外 3D DE 模型中编码胶原蛋白和基质金属蛋白酶组织抑制剂 1 的 mRNAs 的下调。最重要的是，KPA（0.025%）在无毛小鼠背部皮肤的局部应用增强了胶原蛋白的表达，并减轻了 UVB 诱导的 Fn 片段化以及 MMP-2 和 MMP-9 活性的上调。
组织蛋白酶 G 抑制剂可能通过改善 ECM 损伤和 MMP 上调，对预防 UVB 诱导的光老化有用。
