Stress-induced RNASET2 overexpression mediates melanocyte apoptosis via the TRAF2 pathway in vitro.
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.
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Q
Q
Wang
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
M
M
Jiang
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
J
J
Wu
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Y
Y
Ma
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
T
T
Li
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Q
Q
Chen
Institute of Dermatology, Anhui Medical University, Hefei, China.
X
X
Zhang
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
L
L
Xiang
D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism; D011485:Protein Binding; D012260:Ribonucleases / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D047992:TNF Receptor-Associated Factor 2 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*; D014820:Vitiligo / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D055815:Young Adult
D047992:TNF Receptor-Associated Factor 2; D025521:Tumor Suppressor Proteins; D012260:Ribonucleases; C425232:RNASET2 protein, human