Targeted disruption of glutathione peroxidase 4 in mouse skin epithelial cells impairs postnatal hair follicle morphogenesis that is partially rescued through inhibition of COX-2.
Targeted disruption of glutathione peroxidase 4 in mouse skin epithelial cells impairs postnatal hair follicle morphogenesis that is partially rescued through inhibition of COX-2.
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DOI：
10.1038/jid.2013.52
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发表时间：
2013-07
影响因子：
6.5
通讯作者：
Yuspa, Stuart H.
中科院分区：
文献类型：
--
作者：
Sengupta, Aniruddha;Lichti, Ulrike F.;Carlson, Bradley A.;Cataisson, Christophe;Ryscavage, Andrew O.;Mikulec, Carol;Conrad, Marcus;Fischer, Susan M.;Hatfield, Dolph L.;Yuspa, Stuart H.
硒蛋白是哺乳动物抗氧化网络的重要分子。我们之前证明，小鼠表皮中所有硒蛋白的定向损失会破坏皮肤和毛发的发育并导致过早死亡。在当前的研究中，我们针对特定的硒蛋白进行表皮缺失，以确定是否会出现类似的表型。使用 K14-cre 通过 cre-lox 技术生成缺乏谷胱甘肽过氧化物酶 4 (GPx4) 或硫氧还蛋白还原酶 1 (TR1) 基因的角质形成细胞特异性敲除小鼠。 TR1基因敲除小鼠静息皮肤表型正常，而表皮GPx4缺失导致围产期小鼠表皮增生、真皮炎症浸润、毛囊畸形和脱发。与所有硒蛋白的表皮消融不同，GPx4 消融的小鼠在 5 周后恢复并具有正常的寿命。 GPx4 敲除小鼠的皮肤和角质细胞中 GPx1 和 TR1 表达上调。 GPx4 缺失会减少培养物中角质形成细胞的粘附，并增加培养的角质形成细胞和整个皮肤中的脂质过氧化和 COX-2 水平。给哺乳期母亲喂食 COX-2 抑制剂可以部分防止基因敲除幼犬出现异常皮肤表型。这些数据将皮肤 GPx4 的活性与 COX-2 和毛囊形态发生的调节联系起来，并提供了对个体硒蛋白活性在维持皮肤稳态中的功能的深入了解。
Selenoproteins are essential molecules for the mammalian antioxidant network. We previously demonstrated that targeted loss of all selenoproteins in mouse epidermis disrupted skin and hair development and caused premature death. In the current study we targeted specific selenoproteins for epidermal deletion to determine whether similar phenotypes developed. Keratinocyte-specific knockout mice lacking either the glutathione peroxidase 4 (GPx4) or thioredoxin reductase 1 (TR1) gene were generated by cre-lox technology using K14-cre. TR1 knockout mice had a normal phenotype in resting skin while GPx4 loss in epidermis caused epidermal hyperplasia, dermal inflammatory infiltrate, dysmorphic hair follicles and alopecia in perinatal mice. Unlike epidermal ablation of all selenoproteins, mice ablated for GPx4 recovered after 5 weeks and had a normal lifespan. GPx1 and TR1 were upregulated in the skin and keratinocytes of GPx4 knockout mice. GPx4 deletion reduces keratinocyte adhesion in culture and increases lipid peroxidation and COX-2 levels in cultured keratinocytes and whole skin. Feeding a COX-2 inhibitor to nursing mothers partially prevents development of the abnormal skin phenotype in knockout pups. These data link the activity of cutaneous GPx4 to the regulation of COX-2 and hair follicle morphogenesis and provide insight into the function of individual selenoprotein activity in maintaining cutaneous homeostasis.
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影响因子：
56.9
作者：
Kryukov, GV;Castellano, S;Gladyshev, VN
通讯作者：
Gladyshev, VN
影响因子：
5.3
作者：
Conrad, M;Jakupoglu, C;Brielmeier, M
通讯作者：
Brielmeier, M
影响因子：
7
作者：
Cheng, A. W. M.;Bolognesi, M.;Kraus, V. B.
通讯作者：
Kraus, V. B.
DOI：
10.1016/s0006-291x(03)00734-4
发表时间：
2003-05-30
影响因子：
3.1
作者：
Imai, H;Hirao, F;Nakagawa, Y
通讯作者：
Nakagawa, Y
影响因子：
7.4
作者：
Bondareva, Alla A.;Capecchi, Mario R.;Schmidt, Edward E.
通讯作者：
Schmidt, Edward E.