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

Abstract

BackgroundBiliary 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.MethodsThe 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.ResultsThe 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-γ stimulation, which could be suppressed by SOCS1 overexpression. Moreover, miR-155 overexpression activated JAK2/STAT3, thus enhancing the pro-inflammatory effect. Downregulating miR-155 reduced the incidence of BA in a rhesus monkey rotavirus-induced BA model.ConclusionOur results reveal a vital contribution of miR-155 upregulation and consequent SOCS1 downregulation to an immune response triggered via IFN-γ in BA.

• Authors: Rui Zhao, Rui Dong, Yifan Yang, Yuqing Wang, Jin Ma, Jiang Wang, Hao Li, Shan Zheng
• Journal: Pediatric research (Pediatr Res) Vol. 82 Issue 6 Pg. 1007-1016 (Dec 2017) ISSN: 1530-0447 [Electronic] United States
• PMID: 28355202 (Publication Type: Journal Article)

Chemical References

• Inflammation Mediators
• MIRN155 microRNA, human
• MicroRNAs
• SOCS1 protein, human
• Suppressor of Cytokine Signaling 1 Protein

Topics

• Animals
• Animals, Newborn
• Bile Duct Diseases (genetics, metabolism, pathology)
• Biliary Atresia (genetics, metabolism, pathology)
• Case-Control Studies
• Cell Line
• Disease Models, Animal
• Female
• Humans
• Infant
• Infant, Newborn
• Inflammation (genetics, metabolism, pathology)
• Inflammation Mediators (metabolism)
• Mice
• Mice, Inbred BALB C
• MicroRNAs (genetics)
• Pregnancy
• Suppressor of Cytokine Signaling 1 Protein (metabolism)