ArticlePloS one2013
STAT3 regulates MMP3 in heme-induced endothelial cell apoptosis.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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.
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.
Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Cell-based cytokine patch for localized immunomodulation and accelerated healing in rodent and porcine wounds.Nature biomedical engineering · 2026Article
- JAK/STAT inhibition protects glucocorticoid receptor knockout mice from lethal malaria-induced hypoglycemia and hyperinflammation.EMBO molecular medicine · 2025Article
- The SERPINB4 gene mutation identified in twin patients with Crohn's disease impaires the intestinal epithelial cell functions.Scientific reports · 2025Article
- Treadmill Running Regulates Adult Neurogenesis, Spatial and Non-spatial Learning, Parvalbumin Neuron Activity by ErbB4 Signaling.Cellular and molecular neurobiology · 2024Article
- Cerebral microvascular matrix metalloproteinase-3 (MMP3) contributes to vascular injury after stroke in female diabetic rats.Neurochemistry international · 2023Article
- Hsp90 inhibition protects brain endothelial cells against LPS-induced injury.BioFactors (Oxford, England) · 2022Article
- A short deletion in the DNA-binding domain of STAT3 suppresses growth and progression of colon cancer cells.Aging · 2021Article
- TRPM7 Induces Tumorigenesis and Stemness Through Notch Activation in Glioma.Frontiers in pharmacology · 2020Article
- Modelling heme-mediated brain injury associated with cerebral malaria in human brain cortical organoids.Scientific reports · 2019Article
- The impact of endothelial cell death in the brain and its role after stroke: A systematic review.Cell stress · 2019Review
- TRPM7 Induces Mechanistic Target of Rap1b Through the Downregulation of miR-28-5p in Glioma Proliferation and Invasion.Frontiers in oncology · 2019Article
- The long noncoding RNA LOC105374325 causes podocyte injury in individuals with focal segmental glomerulosclerosis.The Journal of biological chemistry · 2018Article
- Neuregulin-1 attenuates experimental cerebral malaria (ECM) pathogenesis by regulating ErbB4/AKT/STAT3 signaling.Journal of neuroinflammation · 2018Article
- Interleukin-10 attenuates impairment of the blood-brain barrier in a severe acute pancreatitis rat model.Journal of inflammation (London, England) · 2018Article
- Article
- Heme-mediated apoptosis and fusion damage in BeWo trophoblast cells.Scientific reports · 2016Article
- Plasmodium-infected erythrocytes (pRBC) induce endothelial cell apoptosis via a heme-mediated signaling pathway.Drug design, development and therapy · 2016Article
- Evodiamine Induces Apoptosis and Inhibits Migration of HCT-116 Human Colorectal Cancer Cells.International journal of molecular sciences · 2015Article
- Article
- Heme-Mediated Induction of CXCL10 and Depletion of CD34+ Progenitor Cells Is Toll-Like Receptor 4 Dependent.PloS one · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundWe have previously reported that free Heme generated during experimental cerebral malaria (ECM) in mice, is central to the pathogenesis of fatal ECM. Heme-induced up-regulation of STAT3 and CXCL10 promotes whereas up-regulation of HO-1 prevents brain tissue damage in ECM. We have previously demonstrated that Heme is involved in the induction of apoptosis in vascular endothelial cells. In the present study, we further tested the hypothesis that Heme reduces blood-brain barrier integrity during ECM by induction of apoptosis of brain vascular endothelial cells through STAT3 and its target gene matrix metalloproteinase three (MMP3) signaling.
methodsGenes associated with the JAK/STAT3 signaling pathway induced upon stimulation by Heme treatment, were assessed using real time RT(2) Profile PCR arrays. A human MMP3 promoter was cloned into a luciferase reporter plasmid, pMMP3, and its activity was examined following exposure to Heme treatment by a luciferase reporter gene assay. In order to determine whether activated nuclear protein STAT3 binds to the MMP3 promoter and regulates MMP3 gene, we conducted a ChIP analysis using Heme-treated and untreated human brain microvascular endothelial cells (HBVEC), and determined mRNA and protein expression levels of MMP3 using qRT-PCR and Western blot. Apoptosis in HBVEC treated with Heme was evaluated by MTT and TUNEL assay.
resultsThe results show that (1) Heme activates a variety of JAK/STAT3 downstream pathways in HBVEC. STAT3 targeted genes such as MMP3 and C/EBPb (Apoptosis-related genes), are up regulated in HBVEC treated with Heme. (2) Heme-induced HBVEC apoptosis via activation of STAT3 as well as its downstream signaling molecule MMP3 and upregulation of CXCL10 and HO-1 expressions. (3) Phosphorylated STAT3 binds to the MMP3 promoter in HBVEC cells, STAT3 transcribed MMP3 and induced MMP3 protein expression in HBVEC cells.
conclusionsActivated STAT3 binds to the MMP3 promoter region and regulates MMP3 in Heme-induced endothelial cell apoptosis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.