CXCL4 Contributes to the Pathogenesis of Chronic Liver Allograft Dysfunction
Chronic liver allograft dysfunction (CLAD) remains the most common cause of patient morbidity and allograft loss in liver transplant patients. However, the pathogenesis of CLAD has not been completely elucidated. By establishing rat CLAD models, in this study, we identified the informative CLAD-asso...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2016/9276986 |
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| author | Jing Li Bin Liu Yuan Shi Ke-Liang Xie Hai-Fang Yin Lu-nan Yan Wan-yee Lau Guo-Lin Wang |
| author_facet | Jing Li Bin Liu Yuan Shi Ke-Liang Xie Hai-Fang Yin Lu-nan Yan Wan-yee Lau Guo-Lin Wang |
| author_sort | Jing Li |
| collection | DOAJ |
| description | Chronic liver allograft dysfunction (CLAD) remains the most common cause of patient morbidity and allograft loss in liver transplant patients. However, the pathogenesis of CLAD has not been completely elucidated. By establishing rat CLAD models, in this study, we identified the informative CLAD-associated genes using isobaric tags for relative and absolute quantification (iTRAQ) proteomics analysis and validated these results in recipient rat liver allografts. CXCL4, CXCR3, EGFR, JAK2, STAT3, and Collagen IV were associated with CLAD pathogenesis. We validated that CXCL4 is upstream of these informative genes in the isolated hepatic stellate cells (HSC). Blocking CXCL4 protects against CLAD by reducing liver fibrosis. Therefore, our results indicated that therapeutic approaches that neutralize CXCL4, a newly identified target of fibrosis, may represent a novel strategy for preventing and treating CLAD after liver transplantation. |
| format | Article |
| id | doaj-art-b51da7c5d66b4ad58dadb46a8a05f6a1 |
| institution | OA Journals |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-b51da7c5d66b4ad58dadb46a8a05f6a12025-08-20T02:23:31ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/92769869276986CXCL4 Contributes to the Pathogenesis of Chronic Liver Allograft DysfunctionJing Li0Bin Liu1Yuan Shi2Ke-Liang Xie3Hai-Fang Yin4Lu-nan Yan5Wan-yee Lau6Guo-Lin Wang7Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin 300052, ChinaDepartment of Critical Care Medicine, General Hospital of Tianjin Medical University, Tianjin 300052, ChinaOrgan Transplantation Center, Tianjin First Center Hospital, Nankai District, Tianjin 300192, ChinaDepartment of Critical Care Medicine, General Hospital of Tianjin Medical University, Tianjin 300052, ChinaDepartment of Cell Biology and Research Center of Basic Medical Science, Tianjin Medical University, Qixiangtai Road, Heping District, Tianjin 300070, ChinaLiver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, ChinaFaculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Sha Tin, Hong KongDepartment of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin 300052, ChinaChronic liver allograft dysfunction (CLAD) remains the most common cause of patient morbidity and allograft loss in liver transplant patients. However, the pathogenesis of CLAD has not been completely elucidated. By establishing rat CLAD models, in this study, we identified the informative CLAD-associated genes using isobaric tags for relative and absolute quantification (iTRAQ) proteomics analysis and validated these results in recipient rat liver allografts. CXCL4, CXCR3, EGFR, JAK2, STAT3, and Collagen IV were associated with CLAD pathogenesis. We validated that CXCL4 is upstream of these informative genes in the isolated hepatic stellate cells (HSC). Blocking CXCL4 protects against CLAD by reducing liver fibrosis. Therefore, our results indicated that therapeutic approaches that neutralize CXCL4, a newly identified target of fibrosis, may represent a novel strategy for preventing and treating CLAD after liver transplantation.http://dx.doi.org/10.1155/2016/9276986 |
| spellingShingle | Jing Li Bin Liu Yuan Shi Ke-Liang Xie Hai-Fang Yin Lu-nan Yan Wan-yee Lau Guo-Lin Wang CXCL4 Contributes to the Pathogenesis of Chronic Liver Allograft Dysfunction Journal of Immunology Research |
| title | CXCL4 Contributes to the Pathogenesis of Chronic Liver Allograft Dysfunction |
| title_full | CXCL4 Contributes to the Pathogenesis of Chronic Liver Allograft Dysfunction |
| title_fullStr | CXCL4 Contributes to the Pathogenesis of Chronic Liver Allograft Dysfunction |
| title_full_unstemmed | CXCL4 Contributes to the Pathogenesis of Chronic Liver Allograft Dysfunction |
| title_short | CXCL4 Contributes to the Pathogenesis of Chronic Liver Allograft Dysfunction |
| title_sort | cxcl4 contributes to the pathogenesis of chronic liver allograft dysfunction |
| url | http://dx.doi.org/10.1155/2016/9276986 |
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