MicroRNA-155 modulates bile duct inflammation by targeting the suppressor of cytokine signaling 1 in biliary atresia

作者：Zhao, Rui; Dong, Rui; Yang, Yifan; Wang, Yuqing; Ma, Jin; Wang, Jiang; Li, Hao; Zheng, Shan^*

来源：Pediatric Research, 2017, 82(6): 1007-1016.

DOI：10.1038/pr.2017.87

• MULTIPLE-SCLEROSIS
• EXPRESSION
• LYMPHOCYTES
• IMMUNOBIOLOGY
• REGULATORS
• PROTEINS
• ETIOLOGY
• ADHESION
• MIR-155

BACKGROUND: Biliary atresia (BA) is an etiologically perplexing disease, manifested by neonatal cholestasis, repeated cholangitis, and progressive biliary fibrosis. MiR-155 has been implicated to modulate the immune response, which contributes to biliary injury. However, its potential role in the pathogenesis of BA has not been addressed so far. @@@ METHODS: The microRNA changes from BA patients and controls were identified via microarray. The immunomodulatory function of miR-155 was investigated via cell transfection and reporter assay. The lentiviral vector pL-miR-155 inhibitor was transfected into a mouse model to investigate its role in BA. @@@ RESULTS: The expression of miR-155 in livers of BA patients was significantly increased, and an inverse correlation between miR-155 and suppressor of cytokine signaling 1 (SOCS1) was detected. MiR-155 overexpression promoted expressions of major histocompatibility complex (MHC) I, MHC II, Chemokine (C-X-C motif) ligand (CXCL) 9, CXCL10, monocyte chemotactic protein 1, and CXCL1 after IFN-gamma stimulation, which could be suppressed by SOCS1 overexpression. Moreover, miR-155 overexpression activated JAK2/STAT3, thus enhancing the pro-inflammatory effect. Down-regulating miR-155 reduced the incidence of BA in a rhesus monkey rotavirus-induced BA model. @@@ CONCLUSION: Our results reveal a vital contribution of miR-155 upregulation and consequent SOCS1 downregulation to an immune response triggered via IFN-gamma in BA.

• 出版日期2017-12
• 单位复旦大学