Evidence map›Paper›PMID 26941017›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2016

Regulation of Vascular Smooth Muscle Cell Dysfunction Under Diabetic Conditions by miR-504.

Marpadga A Reddy, Sadhan Das, Chen Zhuo, Wen Jin, Mei Wang, Linda Lanting, Rama Natarajan

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 7% 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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.

  1. Pooled it
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  9. MicroRNAs in diabetic macroangiopathy.Cardiovascular diabetology · 2024
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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

7 authors at 1 institution in 1 country.

Marpadga A ReddyFrom the Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA.
Sadhan DasFrom the Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA.
Chen ZhuoFrom the Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA.
Wen JinFrom the Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA.
Mei WangFrom the Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA.
Linda LantingFrom the Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA.
Rama NatarajanFrom the Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA. rnatarajan@coh.org mreddy@coh.org.
City of Hope · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
Inflammatory Gene Transcription In Diabetic ConditionsR01DK065073 · NIDDK · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI NATARAJAN, RAMA · 2003 to 2021
$7.9M
Transcriptional Regulation by Angiotensin II in Vascular Smooth Muscle CellsR01HL106089 · NHLBI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI NATARAJAN, RAMA · 2011 to 2024
$6.6M
Epigenetic Markers of Complications and Metabolic Memory in the DCCT/EDIC cohort.DP3DK106917 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI NATARAJAN, RAMA · 2015 to 2015
$2.2M
Nuclear Mechanisms of VSMC Gene Regulation and Cellular Interactions in DiabetesR01HL087864 · NHLBI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI NATARAJAN, RAMA · 2008 to 2012
$2.1M
NCI NIH HHS P30 CA033572NHLBI NIH HHS R01 HL087864NHLBI NIH HHS R01 HL106089NIDDK NIH HHS DP3 DK106917NIDDK NIH HHS R01 DK065073
6 · The paper itself

Abstract

objectiveDiabetes mellitus accelerates proatherogenic and proinflammatory phenotype of vascular smooth muscle cell (VSMC) associated with vascular complications. Evidence shows that microRNAs (miRNAs) play key roles in VSMC functions, but their role under diabetic conditions is unclear. We profiled miRNAs in VSMC from diabetic mice and examined their role in VSMC dysfunction. APPROACH AND

resultsHigh throughput small RNA-sequencing identified 135 differentially expressed miRNAs in VSMC from type 2 diabetic db/db mice (db/dbVSMC) versus nondiabetic db/+ mice. Several of these miRNAs were known to regulate VSMC functions. We further focused on miR-504, because it was highly upregulated in db/dbVSMC, and its function in VSMC is unknown. miR-504 and its host gene Fgf13 were significantly increased in db/dbVSMC and in aortas from db/db mice. Bioinformatics analysis predicted that miR-504 targets including signaling adaptor Grb10 and transcription factor Egr2 could regulate growth factor signaling. We experimentally validated Grb10 and Egr2 as novel targets of miR-504. Overexpression of miR-504 in VSMC inhibited contractile genes and enhanced extracellular signal-regulated kinase 1/2 activation, proliferation, and migration. These effects were blocked by miR-504 inhibitors. Grb10 knockdown mimicked miR-504 functions and increased inflammatory genes. Egr2 knockdown-inhibited anti-inflammatory Socs1 and increased proinflammatory genes. Furthermore, high glucose and palmitic acid upregulated miR-504 and inflammatory genes, but downregulated Grb10.

conclusionsDiabetes mellitus misregulates several miRNAs including miR-504 that can promote VSMC dysfunction. Because changes in many of these miRNAs are sustained in diabetic VSMC even after in vitro culture, they may be involved in metabolic memory of vascular complications. Targeting such mechanisms could offer novel therapeutic strategies for diabetic complications.

Indexed as

AnimalsAorta, ThoracicAortic DiseasesAtherosclerosisCell MovementCell ProliferationCells, CulturedComputational BiologyDiabetes Mellitus, Type 2Diabetic AngiopathiesDisease Models, AnimalEarly Growth Response Protein 2Extracellular Signal-Regulated MAP KinasesFibroblast Growth FactorsGene Expression ProfilingGene Expression RegulationEarly Growth Response Protein 2Egr2 protein, mouseExtracellular Signal-Regulated MAP Kinasesfibroblast growth factor 13Fibroblast Growth FactorsGlucoseGRB10 Adaptor ProteinGrb10 protein, mouseMicroRNAsMIRN504 microRNA, mousePalmitic AcidSocs1 protein, mouseSuppressor of Cytokine Signaling 1 Proteinaortaatherosclerosisdiabetes complicationsinflammationmicroRNAsvascular smooth muscle cells

Identifiers

PMID26941017
PMCPMC4850084
OpenAlexW2291810277

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.