RGD Reference Report - MicroRNA-155 modulates bile duct inflammation by targeting the suppressor of cytokine signaling 1 in biliary atresia. - Rat Genome Database

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

Authors: Zhao, Rui  Dong, Rui  Yang, Yifan  Wang, Yuqing  Ma, Jin  Wang, Jiang  Li, Hao  Zheng, Shan 
Citation: Zhao R, etal., Pediatr Res. 2017 Dec;82(6):1007-1016. doi: 10.1038/pr.2017.87. Epub 2017 Sep 6.
RGD ID: 24922206
Pubmed: PMID:28355202   (View Abstract at PubMed)
DOI: DOI:10.1038/pr.2017.87   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
biliary atresia  IEP 24922206miRNA:increased expression:liverRGD 
biliary atresia  ISOMIR155 (Homo sapiens)24922206; 24922206miRNA:increased expression:liverRGD 

Objects Annotated

Genes (Rattus norvegicus)
Mir155  (microRNA 155)

Genes (Mus musculus)
Mir155  (microRNA 155)

Genes (Homo sapiens)
MIR155  (microRNA 155)


Additional Information