Tumor Necrosis Factor (TNF) Receptor Expression Determines Keratinocyte Fate upon Stimulation with TNF-Like Weak Inducer of Apoptosis
The interaction between tumor necrosis factor- (TNF-) like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible 14 (Fn14) regulates the fate of keratinocytes, depending on the relative expression of TNF receptor (TNFR) 1 or TNFR2. However, the precise mechanism underlying this TW...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2019/2945083 |
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| author | Xuening Wang Dan Cheng Guanglei Hu Lili Liang Fei Tan Tong Xiao Shengxiang Xiao Yumin Xia |
| author_facet | Xuening Wang Dan Cheng Guanglei Hu Lili Liang Fei Tan Tong Xiao Shengxiang Xiao Yumin Xia |
| author_sort | Xuening Wang |
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| description | The interaction between tumor necrosis factor- (TNF-) like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible 14 (Fn14) regulates the fate of keratinocytes, depending on the relative expression of TNF receptor (TNFR) 1 or TNFR2. However, the precise mechanism underlying this TWEAK-mediated regulation remains unclear. The aim of this study was to provide comprehensive insight into the roles of Fn14, TNFR1/2, and other relevant molecules in the fate of keratinocytes. Further, we sought to elucidate the structural basis for the interaction of TWEAK and Fn14 in regulating cellular outcomes. Normal keratinocytes (mainly expressing TNFR1) and TNFR2-overexpressing keratinocytes were stimulated with TWEAK. Through immunoprecipitation and Western blotting of keratinocyte lysates, we elucidated the associations between Fn14, TNFR-associated factor 2 (TRAF2), cellular inhibitor of apoptosis protein 1 (cIAP1), and TNFR1/2 molecules. Additionally, we found that TRAF2 exhibited binding to Fn14, cIAP1, and TNFR1/2. Our data suggest that TWEAK induces apoptosis in normal keratinocytes and proliferation in TNFR2-overexpressing keratinocytes in a TNF-α-independent manner; however, inhibition of TRAF2 appears to reverse this effect. Interestingly, the interaction between TWEAK and Fn14 increased TNFR1-associated death domain protein and caspase-8 expression in normal keratinocytes and promoted cytoplasmic import of cIAP1 in TNFR2-overexpressing keratinocytes. In conclusion, we found that the Fn14-TRAF2-TNFR signaling axis mediates TWEAK’s regulation of the fate of keratinocytes, possibly in a manner involving the TNF-α-independent TNFR signal transduction. |
| format | Article |
| id | doaj-art-663de01f2dcc41f8b86b1eb926bcb5ed |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-663de01f2dcc41f8b86b1eb926bcb5ed2025-02-03T06:05:25ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/29450832945083Tumor Necrosis Factor (TNF) Receptor Expression Determines Keratinocyte Fate upon Stimulation with TNF-Like Weak Inducer of ApoptosisXuening Wang0Dan Cheng1Guanglei Hu2Lili Liang3Fei Tan4Tong Xiao5Shengxiang Xiao6Yumin Xia7Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaCollege of Life Sciences, Wuhan University, Wuhan, ChinaDepartment of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaThe interaction between tumor necrosis factor- (TNF-) like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible 14 (Fn14) regulates the fate of keratinocytes, depending on the relative expression of TNF receptor (TNFR) 1 or TNFR2. However, the precise mechanism underlying this TWEAK-mediated regulation remains unclear. The aim of this study was to provide comprehensive insight into the roles of Fn14, TNFR1/2, and other relevant molecules in the fate of keratinocytes. Further, we sought to elucidate the structural basis for the interaction of TWEAK and Fn14 in regulating cellular outcomes. Normal keratinocytes (mainly expressing TNFR1) and TNFR2-overexpressing keratinocytes were stimulated with TWEAK. Through immunoprecipitation and Western blotting of keratinocyte lysates, we elucidated the associations between Fn14, TNFR-associated factor 2 (TRAF2), cellular inhibitor of apoptosis protein 1 (cIAP1), and TNFR1/2 molecules. Additionally, we found that TRAF2 exhibited binding to Fn14, cIAP1, and TNFR1/2. Our data suggest that TWEAK induces apoptosis in normal keratinocytes and proliferation in TNFR2-overexpressing keratinocytes in a TNF-α-independent manner; however, inhibition of TRAF2 appears to reverse this effect. Interestingly, the interaction between TWEAK and Fn14 increased TNFR1-associated death domain protein and caspase-8 expression in normal keratinocytes and promoted cytoplasmic import of cIAP1 in TNFR2-overexpressing keratinocytes. In conclusion, we found that the Fn14-TRAF2-TNFR signaling axis mediates TWEAK’s regulation of the fate of keratinocytes, possibly in a manner involving the TNF-α-independent TNFR signal transduction.http://dx.doi.org/10.1155/2019/2945083 |
| spellingShingle | Xuening Wang Dan Cheng Guanglei Hu Lili Liang Fei Tan Tong Xiao Shengxiang Xiao Yumin Xia Tumor Necrosis Factor (TNF) Receptor Expression Determines Keratinocyte Fate upon Stimulation with TNF-Like Weak Inducer of Apoptosis Mediators of Inflammation |
| title | Tumor Necrosis Factor (TNF) Receptor Expression Determines Keratinocyte Fate upon Stimulation with TNF-Like Weak Inducer of Apoptosis |
| title_full | Tumor Necrosis Factor (TNF) Receptor Expression Determines Keratinocyte Fate upon Stimulation with TNF-Like Weak Inducer of Apoptosis |
| title_fullStr | Tumor Necrosis Factor (TNF) Receptor Expression Determines Keratinocyte Fate upon Stimulation with TNF-Like Weak Inducer of Apoptosis |
| title_full_unstemmed | Tumor Necrosis Factor (TNF) Receptor Expression Determines Keratinocyte Fate upon Stimulation with TNF-Like Weak Inducer of Apoptosis |
| title_short | Tumor Necrosis Factor (TNF) Receptor Expression Determines Keratinocyte Fate upon Stimulation with TNF-Like Weak Inducer of Apoptosis |
| title_sort | tumor necrosis factor tnf receptor expression determines keratinocyte fate upon stimulation with tnf like weak inducer of apoptosis |
| url | http://dx.doi.org/10.1155/2019/2945083 |
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