Fn14 Deficiency Ameliorates Anti-dsDNA IgG-Induced Glomerular Damage in SCID Mice
Many studies have demonstrated that anti-dsDNA IgG is closely associated with lupus nephritis. Recently, it was found that activation of the fibroblast growth factor-inducible 14 (Fn14) signaling pathway damages glomerular filtration barrier in MRL/lpr lupus-prone mice. However, MRL/lpr mice have hi...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2018/1256379 |
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| author | Jiawen Wu Xiaoyun Min Li Wang Jie Yang Ping Wang Xingyin Liu Yumin Xia |
| author_facet | Jiawen Wu Xiaoyun Min Li Wang Jie Yang Ping Wang Xingyin Liu Yumin Xia |
| author_sort | Jiawen Wu |
| collection | DOAJ |
| description | Many studies have demonstrated that anti-dsDNA IgG is closely associated with lupus nephritis. Recently, it was found that activation of the fibroblast growth factor-inducible 14 (Fn14) signaling pathway damages glomerular filtration barrier in MRL/lpr lupus-prone mice. However, MRL/lpr mice have high titers of serum autoantibodies other than anti-dsDNA IgG. The aim of this study was to further explore the effect of Fn14 deficiency on anti-dsDNA IgG-induced glomerular damage in severe combined immunodeficiency (SCID) mice that have no endogenous IgG. Fn14 deficiency was generated in SCID mice. The murine hybridoma cells producing control IgG or anti-dsDNA IgG were intraperitoneally injected into mice. In two weeks, the urine, serum, and kidney tissue samples were harvested from mice at sacrifice. It showed that the injection of anti-dsDNA IgG, but not control IgG hybridoma cells, induced proteinuria and glomerular damage in SCID mice. Between the wild-type (WT) and knockout (KO) mice injected with anti-dsDNA IgG hybridoma cells, the latter showed a decrease in both proteinuria and glomerular IgG deposition. The histopathological changes, inflammatory cell infiltration, and proinflammatory cytokine production were also attenuated in the kidneys of the Fn14-KO mice upon anti-dsDNA IgG injection. Therefore, Fn14 deficiency effectively protects SCID mice from anti-dsDNA IgG-induced glomerular damage. |
| format | Article |
| id | doaj-art-7f0956e66dfc403db3556e0185e792b4 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-7f0956e66dfc403db3556e0185e792b42025-02-03T07:25:26ZengWileyJournal of Immunology Research2314-88612314-71562018-01-01201810.1155/2018/12563791256379Fn14 Deficiency Ameliorates Anti-dsDNA IgG-Induced Glomerular Damage in SCID MiceJiawen Wu0Xiaoyun Min1Li Wang2Jie Yang3Ping Wang4Xingyin Liu5Yumin Xia6Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710004, ChinaCore Research Laboratory, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710004, ChinaDepartment of Nephrology, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710004, ChinaDepartment of Nephrology, Tangdu Hospital, Air Force Military Medical University, Xi’an 710038, ChinaDepartment of Immunology and Microbiology, Wannan Medical College, Wuhu 241002, ChinaDepartment of Pathogenic Biology, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710004, ChinaMany studies have demonstrated that anti-dsDNA IgG is closely associated with lupus nephritis. Recently, it was found that activation of the fibroblast growth factor-inducible 14 (Fn14) signaling pathway damages glomerular filtration barrier in MRL/lpr lupus-prone mice. However, MRL/lpr mice have high titers of serum autoantibodies other than anti-dsDNA IgG. The aim of this study was to further explore the effect of Fn14 deficiency on anti-dsDNA IgG-induced glomerular damage in severe combined immunodeficiency (SCID) mice that have no endogenous IgG. Fn14 deficiency was generated in SCID mice. The murine hybridoma cells producing control IgG or anti-dsDNA IgG were intraperitoneally injected into mice. In two weeks, the urine, serum, and kidney tissue samples were harvested from mice at sacrifice. It showed that the injection of anti-dsDNA IgG, but not control IgG hybridoma cells, induced proteinuria and glomerular damage in SCID mice. Between the wild-type (WT) and knockout (KO) mice injected with anti-dsDNA IgG hybridoma cells, the latter showed a decrease in both proteinuria and glomerular IgG deposition. The histopathological changes, inflammatory cell infiltration, and proinflammatory cytokine production were also attenuated in the kidneys of the Fn14-KO mice upon anti-dsDNA IgG injection. Therefore, Fn14 deficiency effectively protects SCID mice from anti-dsDNA IgG-induced glomerular damage.http://dx.doi.org/10.1155/2018/1256379 |
| spellingShingle | Jiawen Wu Xiaoyun Min Li Wang Jie Yang Ping Wang Xingyin Liu Yumin Xia Fn14 Deficiency Ameliorates Anti-dsDNA IgG-Induced Glomerular Damage in SCID Mice Journal of Immunology Research |
| title | Fn14 Deficiency Ameliorates Anti-dsDNA IgG-Induced Glomerular Damage in SCID Mice |
| title_full | Fn14 Deficiency Ameliorates Anti-dsDNA IgG-Induced Glomerular Damage in SCID Mice |
| title_fullStr | Fn14 Deficiency Ameliorates Anti-dsDNA IgG-Induced Glomerular Damage in SCID Mice |
| title_full_unstemmed | Fn14 Deficiency Ameliorates Anti-dsDNA IgG-Induced Glomerular Damage in SCID Mice |
| title_short | Fn14 Deficiency Ameliorates Anti-dsDNA IgG-Induced Glomerular Damage in SCID Mice |
| title_sort | fn14 deficiency ameliorates anti dsdna igg induced glomerular damage in scid mice |
| url | http://dx.doi.org/10.1155/2018/1256379 |
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