Upregulation of KSRP by miR-27b provides IFNγ-induced post-transcriptional regulation of CX3CL1 in liver epithelial cells

Zijie Xia, Yajing Lu, Xiaoqing Li, Tiebo Mao, Xian-Ming Chen, Rui Zhou

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Aberrant cellular responses to pro-inflammatory cytokines, such as IFN-γ, are pathogenic features in many chronic inflammatory diseases. A variety of feedback regulatory pathways have evolved to prevent an inappropriate cellular reaction to these pro-inflammatory cytokines. CX3CL1 is a unique chemokine and plays an important role in chronic liver diseases. We report here that IFN-γ stimulation induces a transient CX3CL1 production in liver epithelial cells (i.e., hepatocytes and biliary epithelial cells). This transient CX3CL1 production is accompanied with a destabilization of CX3CL1 mRNA associated with the induction of the KH-type splicing regulatory protein (KSRP). IFN-γ treatment of liver epithelial cells decreases expression level of miR-27b, a miRNA that targets the 3′ untranslated region of KSRP mRNA resulting in translational suppression. Induction of KSRP following IFN-γ stimulation depends on the downregulation of miR-27b. Functional manipulation of KSRP or miR-27b caused reciprocal alterations in CX3CL1 mRNA stability in liver epithelial cells. Moreover, transfection of miR-27b precursor influences CX3CL1-associated chemotaxis effects of biliary epithelial cells to Jurkat T cells. These findings suggest that miR-27b-mediated post-transcriptional suppression controls the expression of KSRP in liver epithelial cells, and upregulation of KSRP destabilizes CX3CL1 mRNA, providing fine-tuning of cellular inflammatory reactions in response to IFN-γ stimulation.

Original languageEnglish
Article number17590
JournalScientific Reports
Volume5
DOIs
StatePublished - Dec 3 2015

Fingerprint

Protein Splicing
Up-Regulation
Epithelial Cells
Liver
Messenger RNA
Chronic Disease
Cytokines
Jurkat Cells
RNA Stability
3' Untranslated Regions
Chemotaxis
MicroRNAs
Chemokines
Transfection
Liver Diseases
Hepatocytes
Down-Regulation
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Upregulation of KSRP by miR-27b provides IFNγ-induced post-transcriptional regulation of CX3CL1 in liver epithelial cells. / Xia, Zijie; Lu, Yajing; Li, Xiaoqing; Mao, Tiebo; Chen, Xian-Ming; Zhou, Rui.

In: Scientific Reports, Vol. 5, 17590, 03.12.2015.

Research output: Contribution to journalArticle

@article{0efb4a57e2fe4cc8a062beed363d1653,
title = "Upregulation of KSRP by miR-27b provides IFNγ-induced post-transcriptional regulation of CX3CL1 in liver epithelial cells",
abstract = "Aberrant cellular responses to pro-inflammatory cytokines, such as IFN-γ, are pathogenic features in many chronic inflammatory diseases. A variety of feedback regulatory pathways have evolved to prevent an inappropriate cellular reaction to these pro-inflammatory cytokines. CX3CL1 is a unique chemokine and plays an important role in chronic liver diseases. We report here that IFN-γ stimulation induces a transient CX3CL1 production in liver epithelial cells (i.e., hepatocytes and biliary epithelial cells). This transient CX3CL1 production is accompanied with a destabilization of CX3CL1 mRNA associated with the induction of the KH-type splicing regulatory protein (KSRP). IFN-γ treatment of liver epithelial cells decreases expression level of miR-27b, a miRNA that targets the 3′ untranslated region of KSRP mRNA resulting in translational suppression. Induction of KSRP following IFN-γ stimulation depends on the downregulation of miR-27b. Functional manipulation of KSRP or miR-27b caused reciprocal alterations in CX3CL1 mRNA stability in liver epithelial cells. Moreover, transfection of miR-27b precursor influences CX3CL1-associated chemotaxis effects of biliary epithelial cells to Jurkat T cells. These findings suggest that miR-27b-mediated post-transcriptional suppression controls the expression of KSRP in liver epithelial cells, and upregulation of KSRP destabilizes CX3CL1 mRNA, providing fine-tuning of cellular inflammatory reactions in response to IFN-γ stimulation.",
author = "Zijie Xia and Yajing Lu and Xiaoqing Li and Tiebo Mao and Xian-Ming Chen and Rui Zhou",
year = "2015",
month = "12",
day = "3",
doi = "10.1038/srep17590",
language = "English",
volume = "5",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Upregulation of KSRP by miR-27b provides IFNγ-induced post-transcriptional regulation of CX3CL1 in liver epithelial cells

AU - Xia, Zijie

AU - Lu, Yajing

AU - Li, Xiaoqing

AU - Mao, Tiebo

AU - Chen, Xian-Ming

AU - Zhou, Rui

PY - 2015/12/3

Y1 - 2015/12/3

N2 - Aberrant cellular responses to pro-inflammatory cytokines, such as IFN-γ, are pathogenic features in many chronic inflammatory diseases. A variety of feedback regulatory pathways have evolved to prevent an inappropriate cellular reaction to these pro-inflammatory cytokines. CX3CL1 is a unique chemokine and plays an important role in chronic liver diseases. We report here that IFN-γ stimulation induces a transient CX3CL1 production in liver epithelial cells (i.e., hepatocytes and biliary epithelial cells). This transient CX3CL1 production is accompanied with a destabilization of CX3CL1 mRNA associated with the induction of the KH-type splicing regulatory protein (KSRP). IFN-γ treatment of liver epithelial cells decreases expression level of miR-27b, a miRNA that targets the 3′ untranslated region of KSRP mRNA resulting in translational suppression. Induction of KSRP following IFN-γ stimulation depends on the downregulation of miR-27b. Functional manipulation of KSRP or miR-27b caused reciprocal alterations in CX3CL1 mRNA stability in liver epithelial cells. Moreover, transfection of miR-27b precursor influences CX3CL1-associated chemotaxis effects of biliary epithelial cells to Jurkat T cells. These findings suggest that miR-27b-mediated post-transcriptional suppression controls the expression of KSRP in liver epithelial cells, and upregulation of KSRP destabilizes CX3CL1 mRNA, providing fine-tuning of cellular inflammatory reactions in response to IFN-γ stimulation.

AB - Aberrant cellular responses to pro-inflammatory cytokines, such as IFN-γ, are pathogenic features in many chronic inflammatory diseases. A variety of feedback regulatory pathways have evolved to prevent an inappropriate cellular reaction to these pro-inflammatory cytokines. CX3CL1 is a unique chemokine and plays an important role in chronic liver diseases. We report here that IFN-γ stimulation induces a transient CX3CL1 production in liver epithelial cells (i.e., hepatocytes and biliary epithelial cells). This transient CX3CL1 production is accompanied with a destabilization of CX3CL1 mRNA associated with the induction of the KH-type splicing regulatory protein (KSRP). IFN-γ treatment of liver epithelial cells decreases expression level of miR-27b, a miRNA that targets the 3′ untranslated region of KSRP mRNA resulting in translational suppression. Induction of KSRP following IFN-γ stimulation depends on the downregulation of miR-27b. Functional manipulation of KSRP or miR-27b caused reciprocal alterations in CX3CL1 mRNA stability in liver epithelial cells. Moreover, transfection of miR-27b precursor influences CX3CL1-associated chemotaxis effects of biliary epithelial cells to Jurkat T cells. These findings suggest that miR-27b-mediated post-transcriptional suppression controls the expression of KSRP in liver epithelial cells, and upregulation of KSRP destabilizes CX3CL1 mRNA, providing fine-tuning of cellular inflammatory reactions in response to IFN-γ stimulation.

UR - http://www.scopus.com/inward/record.url?scp=84949310103&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84949310103&partnerID=8YFLogxK

U2 - 10.1038/srep17590

DO - 10.1038/srep17590

M3 - Article

VL - 5

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 17590

ER -