ArticleJournal of molecular medicine (Berlin, Germany)2014
The signal transducers Stat1 and Stat3 and their novel target Jmjd3 drive the expression of inflammatory genes in microglia.
Article in Journal of molecular medicine (Berlin, Germany), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 190 citations in OpenAlex.
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- A multi-omic atlas in the African turquoise killifish reveals increased glucocorticoid signaling as a hallmark of brain aging.bioRxiv : the preprint server for biology · 2026Article
- A critical role for STAT3 Thr714 phosphorylation in NPM-ALK-driven tumorigenesis.Scientific reports · 2026Article
- Genetic and environmental drivers of sex determination in turtles: insights and implications for conservation.Molecular biology reports · 2026Review
- hsa_circ_0006168 drives microglial activation in TNC via miR-99b-5p/KDM6B axis to promote central sensitization in migraine.The journal of headache and pain · 2026Article
- Social hierarchy and resilience affect stress-induced PTSD via Uba7 gene expression and subsequent inflammation in microglia of the mPFC.Molecular psychiatry · 2026Article
- Imatinib prevents blood-spinal cord barrier disruption by inhibiting PDGFR-mediated JMJD3 expression and activation after spinal cord injury.Fluids and barriers of the CNS · 2025Article
- MicroRNAs Modulating Neuroinflammation in Parkinson's disease.Inflammation · 2025Review
- The intersection of endocrine signaling and neuroimmune communication regulates muscle inflammation-induced nociception in neonatal mice.Brain, behavior, and immunity · 2025Article
- Unraveling the role of Nrf2 in dopaminergic neurons: a review of oxidative stress and mitochondrial dysfunction in Parkinson's disease.Metabolic brain disease · 2025Review
- Lanreotide protects against LPS-induced inflammation in endothelial cells and mouse lungs.Tissue barriers · 2025Article
- Is postoperative cognitive dysfunction a disease of microglial inflammatory memory? A state-transition model from metabolic stress to epigenetic lock-in.Frontiers in molecular neuroscience · 2025Review
- JMJD3 deficiency disturbs dopamine biosynthesis in midbrain and aggravates chronic inflammatory pain.Acta neuropathologica communications · 2024Article
- Article
- Rab8a/SNARE complex activation promotes vesicle anchoring and transport in spinal astrocytes to drive neuropathic pain.Biomolecules & biomedicine · 2024Article
- Emerging role of Jumonji domain-containing protein D3 in inflammatory diseases.Journal of pharmaceutical analysis · 2024Review
- Identification of Parkinson's disease PACE subtypes and repurposing treatments through integrative analyses of multimodal data.NPJ digital medicine · 2024Article
- Recent Advances and Therapeutic Implications of 2-Oxoglutarate-Dependent Dioxygenases in Ischemic Stroke.Molecular neurobiology · 2024Review
- Neuroinflammatory gene expression profiles of reactive glia in the substantia nigra suggest a multidimensional immune response to alpha synuclein inclusions.Neurobiology of disease · 2024Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledMost neurological diseases are associated with chronic inflammation initiated by the activation of microglia, which produce cytotoxic and inflammatory factors. Signal transducers and activators of transcription (STATs) are potent regulators of gene expression but contribution of particular STAT to inflammatory gene expression and STAT-dependent transcriptional networks underlying brain inflammation need to be identified. In the present study, we investigated the genomic distribution of Stat binding sites and the role of Stats in the gene expression in lipopolysaccharide (LPS)-activated primary microglial cultures. Integration of chromatin immunoprecipitation-promoter microarray data and transcriptome data revealed novel Stat-target genes including Jmjd3, Ccl5, Ezr, Ifih1, Irf7, Uba7, and Pim1. While knockdown of individual Stat had little effect on the expression of tested genes, knockdown of both Stat1 and Stat3 inhibited the expression of Jmjd3 and inflammatory genes. Transcriptional regulation of Jmjd3 by Stat1 and Stat3 is a novel mechanism crucial for launching inflammatory responses in microglia. The effects of Jmjd3 on inflammatory gene expression were independent of its H3K27me3 demethylase activity. Forced expression of constitutively activated Stat1 and Stat3 induced the expression of Jmjd3, inflammation-related genes, and the production of pro-inflammatory cytokines as potently as lipopolysacharide. Gene set enrichment and gene function analysis revealed categories linked to the inflammatory response in LPS and Stat1C + Stat3C groups. We defined upstream pathways that activate STATs in response to LPS and demonstrated contribution of Tlr4 and Il-6 and interferon-γ signaling. Our findings define novel direct transcriptional targets of Stat1 and Stat3 and highlight their contribution to inflammatory gene expression. KEY MESSAGE: Combined analysis of genomic Stat occupancy and transcriptome revealed novel Stat target genes in LPS-induced microglia. Jmjd3 transcription factor is a novel transcriptional target of Stat1 and Stat3. Stat1 and Stat3 cooperate with Jmjd3 to induce the expression of pro-inflammatory genes. Constitutively active Stat1 and Stat3 fully mimic the LPS-induced upregulation of inflammatory genes and secretion of cytokines.
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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.