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CXCL4 Contributes to the Pathogenesis of Chronic Liver Allograft Dysfunction
oleh: Jing Li, Bin Liu, Yuan Shi, Ke-Liang Xie, Hai-Fang Yin, Lu-nan Yan, Wan-yee Lau, Guo-Lin Wang
Format: | Article |
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Diterbitkan: | Wiley 2016-01-01 |
Deskripsi
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.