Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Accelerates the Progression of Renal Fibrosis in Lupus Nephritis by Activating SMAD and p38 MAPK in TGF-β1 Signaling Pathway
This study aim was to explore the effects of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in lupus nephritis and its potential underlying mechanisms. MRL/lpr mice were used for in vivo experiments and human proximal tubular cells (HK2 cells) were used for in vitro experiments. Result...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/8986451 |
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| author | Zhiqin Liu Leixi Xue Zhichun Liu Jun Huang Jian Wen Ji Hu Lin Bo Ru Yang |
| author_facet | Zhiqin Liu Leixi Xue Zhichun Liu Jun Huang Jian Wen Ji Hu Lin Bo Ru Yang |
| author_sort | Zhiqin Liu |
| collection | DOAJ |
| description | This study aim was to explore the effects of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in lupus nephritis and its potential underlying mechanisms. MRL/lpr mice were used for in vivo experiments and human proximal tubular cells (HK2 cells) were used for in vitro experiments. Results showed that MRL/lpr mice treated with vehicle solution or LV-Control shRNA displayed significant proteinuria and severe renal histopathological changes. LV-TWEAK-shRNA treatment reversed these changes and decreased renal expressions of TWEAK, TGF-β1, p-p38 MAPK, p-Smad2, COL-1, and α-SMA proteins. In vitro, hTWEAK treatment upregulated the expressions of TGF-β1, p-p38 MAPK, p-SMAD2, α-SMA, and COL-1 proteins in HK2 cells and downregulated the expressions of E-cadherin protein, which were reversed by cotreatment with anti-TWEAK mAb or SB431542 treatment. These findings suggest that TWEAK may contribute to chronic renal changes and renal fibrosis by activating TGF-β1 signaling pathway, and phosphorylation of Smad2 and p38 MAPK proteins was also involved in this signaling pathway. |
| format | Article |
| id | doaj-art-08493d65f2c74608b9182b25f4e5a55a |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-08493d65f2c74608b9182b25f4e5a55a2025-08-20T03:55:32ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/89864518986451Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Accelerates the Progression of Renal Fibrosis in Lupus Nephritis by Activating SMAD and p38 MAPK in TGF-β1 Signaling PathwayZhiqin Liu0Leixi Xue1Zhichun Liu2Jun Huang3Jian Wen4Ji Hu5Lin Bo6Ru Yang7Department of Biological Science & Engineering, Hebei University of Science & Technology, Shijiazhuang 050018, ChinaDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, ChinaDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, ChinaDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, ChinaDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, ChinaDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, ChinaDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, ChinaDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, ChinaThis study aim was to explore the effects of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in lupus nephritis and its potential underlying mechanisms. MRL/lpr mice were used for in vivo experiments and human proximal tubular cells (HK2 cells) were used for in vitro experiments. Results showed that MRL/lpr mice treated with vehicle solution or LV-Control shRNA displayed significant proteinuria and severe renal histopathological changes. LV-TWEAK-shRNA treatment reversed these changes and decreased renal expressions of TWEAK, TGF-β1, p-p38 MAPK, p-Smad2, COL-1, and α-SMA proteins. In vitro, hTWEAK treatment upregulated the expressions of TGF-β1, p-p38 MAPK, p-SMAD2, α-SMA, and COL-1 proteins in HK2 cells and downregulated the expressions of E-cadherin protein, which were reversed by cotreatment with anti-TWEAK mAb or SB431542 treatment. These findings suggest that TWEAK may contribute to chronic renal changes and renal fibrosis by activating TGF-β1 signaling pathway, and phosphorylation of Smad2 and p38 MAPK proteins was also involved in this signaling pathway.http://dx.doi.org/10.1155/2016/8986451 |
| spellingShingle | Zhiqin Liu Leixi Xue Zhichun Liu Jun Huang Jian Wen Ji Hu Lin Bo Ru Yang Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Accelerates the Progression of Renal Fibrosis in Lupus Nephritis by Activating SMAD and p38 MAPK in TGF-β1 Signaling Pathway Mediators of Inflammation |
| title | Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Accelerates the Progression of Renal Fibrosis in Lupus Nephritis by Activating SMAD and p38 MAPK in TGF-β1 Signaling Pathway |
| title_full | Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Accelerates the Progression of Renal Fibrosis in Lupus Nephritis by Activating SMAD and p38 MAPK in TGF-β1 Signaling Pathway |
| title_fullStr | Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Accelerates the Progression of Renal Fibrosis in Lupus Nephritis by Activating SMAD and p38 MAPK in TGF-β1 Signaling Pathway |
| title_full_unstemmed | Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Accelerates the Progression of Renal Fibrosis in Lupus Nephritis by Activating SMAD and p38 MAPK in TGF-β1 Signaling Pathway |
| title_short | Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Accelerates the Progression of Renal Fibrosis in Lupus Nephritis by Activating SMAD and p38 MAPK in TGF-β1 Signaling Pathway |
| title_sort | tumor necrosis factor like weak inducer of apoptosis accelerates the progression of renal fibrosis in lupus nephritis by activating smad and p38 mapk in tgf β1 signaling pathway |
| url | http://dx.doi.org/10.1155/2016/8986451 |
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