Evidence map›Paper›PMID 27215284›Full record

ArticleBMC pulmonary medicine2016

The MK2/HuR signaling pathway regulates TNF-α-induced ICAM-1 expression by promoting the stabilization of ICAM-1 mRNA.

Ting Wu, Jia-Xin Shi, Shen Geng, Wei Zhou, Yi Shi, Xin Su

Open access · goldAbstract read
In one paragraph

Article in BMC pulmonary medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 16 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Ting WuDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210002, China.
Jia-Xin ShiDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210002, China.
Shen GengDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Southern Medical University, Guangdong, 510000, China.
Wei ZhouDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210002, China.
Yi ShiDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210002, China. shiyi56@126.com.
Xin SuDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210002, China. suxinjs@163.com.
Nanjing University · CNNanjing General Hospital of Nanjing Military Command · CNSouthern Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by acute lung inflammation. Intercellular adhesion molecule-1 (ICAM-1) and interleukin-8 (IL-8) play an important role in the development of these diseases. Mitogen-activated protein kinase (MAPK) p38/activated protein kinase 2 (MK2) regulates the expression of ICAM-1 and IL-8 in human lung microvascular endothelial cells (HPMECs) stimulated by tumor necrosis factor-α (TNF-α); however, the underlying molecular mechanism remains unclear. Here, we show that human antigen R (HuR), an RNA binding protein which binds preferentially to AU-rich elements (AREs) and stabilizes mRNAs, regulates TNF-α-induced ICAM-1 expression in the MK2/HuR signaling pathway.

methodMK2 and HuR were silenced respectively in HPMECs and then HPMECs were stimulatied with TNF-α. Nucleo-cytoplasmic shuttling of HuR was detected by subcellular fractionation and confocal microscopy in MK2 knockdown HPMECs. In HuR silencing cells, protein and mRNA levels of ICAM-1 and IL-8 were measured by western blot analysis, ELISA and real-time PCR; mRNA stabilization were measured by real-time PCR after actinomycin D (ActD) blocking transcription. Furthermore, we performed neutrophil adhesion assay to assess the adhering capacity after HuR silencing.

resultsMK2 were subjected to a knockdown by interfering RNA, the mRNA and protein levels of HuR in human pulmonary microvascular endothelial cells (HPMECs) were not affected. However, after the stimulation of TNF-α, silencing MK2 inhibited HuR accumulation to cytoplasm from nucleus in HPMECs. Consequently, knockdown of HuR by RNA interference in HPMECs, there was reduction in the stability of ICAM-1 mRNA and ICAM-1 protein level. This event was accompanied by a decrease in the adhesion of neutrophils towards HPMECs. Nevertheless, HuR silencing had no effect on the mRNA and protein levels of IL-8.

conclusionThese results indicate that MK2 post-transcriptionally regulates TNF-α-induced ICAM-1 expression by altering the cytoplasmic localization of HuR in HPMECs.

Indexed as

Signal TransductionCells, CulturedELAV-Like Protein 1Endothelial CellsGene Expression RegulationGene Knockdown TechniquesHumansIntercellular Adhesion Molecule-1Interleukin-8Intracellular Signaling Peptides and ProteinsMAP-Kinase-Activated Kinase 2Protein Serine-Threonine KinasesRNA InterferenceRNA, MessengerTumor Necrosis Factor-alphaCXCL8 protein, humanELAVL1 protein, humanELAV-Like Protein 1Intercellular Adhesion Molecule-1Interleukin-8Intracellular Signaling Peptides and ProteinsMAP-Kinase-Activated Kinase 2Protein Serine-Threonine KinasesRNA, MessengerTumor Necrosis Factor-alphaHPMECHuRICAM-1IL-8MK2

Identifiers

PMID27215284
PMCPMC4877999
OpenAlexW2395030726

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.