Stress-induced RNASET2 overexpression mediates melanocyte apoptosis via the TRAF2 pathway in vitro.
Stress-induced RNASET2 overexpression mediates melanocyte apoptosis via the TRAF2 pathway in vitro.
复制标题
压力诱导的 RNASET2 过表达在体外通过 TRAF2 途径介导黑素细胞凋亡。
DOI：
10.1038/cddis.2013.539
复制
发表时间：
2014-01-23
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
最近的全基因组关联研究确定了白癜风与核糖核酸酶 T2 (RNASET2) 基因的遗传变异之间的联系；然而，RNASET2 在白癜风发病机制或黑素细胞凋亡中的功能作用尚未确定。本研究旨在探讨RNASET2与白癜风相关的表达模式及其涉及凋亡相关信号蛋白和通路的分子功能。结果显示，与匹配的健康对照相比，40 名白癜风患者的表皮标本中 RNASET2 过度表达。此外，体外分析表明，应激条件（即分别暴露于紫外线照射、过氧化氢和炎症因子）可诱导培养的原代人黑素细胞和角质形成细胞中RNASET2的过度表达，并通过RNASET2与TRAF2的物理相互作用，通过肿瘤坏死因子受体相关因子2（TRAF2）-半胱天冬酶途径导致细胞凋亡增加。因此，RNASET2可能通过抑制TRAF2表达而促进白癜风发病机制，因此，RNASET2可能代表白癜风的潜在治疗靶点。
The recent genome-wide association study identified a link between vitiligo and genetic variants in the ribonuclease T2 (RNASET2) gene; however, the functional roles of RNASET2 in vitiligo pathogenesis or in melanocyte apoptosis have yet to be determined. The current study was designed to investigate the vitiligo-related expression pattern of RNASET2 and its molecular function involving apoptosis-related signaling proteins and pathways. The results showed overexpression of RNASET2 in epidermis specimens from 40 vitiligo patients compared with that from matched healthy controls. In addition, in vitro analyses indicated that overexpression of RNASET2 was inducible in cultured primary human melanocytes and keratinocytes by stress conditions, that is, exposure to UV irradiation, hydrogen peroxide, and inflammatory factors, respectively, and led to increased cell apoptosis via the tumor necrosis factor receptor-associated factor 2 (TRAF2)–caspases pathway through the physical interaction of RNASET2 with TRAF2. Thus, RNASET2 may contribute to vitiligo pathogenesis by inhibiting TRAF2 expression and, as such, RNASET2 may represent a potential therapeutic target of vitiligo.
登录
查看更多内容
影响因子：
4.5
作者：
Thompson, Debrah M.;Lu, Cheng;Parker, Roy
通讯作者：
Parker, Roy
影响因子：
11.2
作者：
Kadekaro, AL;Kavanagh, R;Abdel-Malek, ZA
通讯作者：
Abdel-Malek, ZA
影响因子：
4.8
作者：
Böhm, M;Wolff, I;Schwarz, A
通讯作者：
Schwarz, A
影响因子：
14.9
作者：
Thorn A;Steinfeld R;Ziegenbein M;Grapp M;Hsiao HH;Urlaub H;Sheldrick GM;Gärtner J;Krätzner R
通讯作者：
Krätzner R
影响因子：
158.5
作者：
Taieb, Alain;Picardo, Mauro
通讯作者：
Picardo, Mauro