ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2021
BHLHE40 promotes macrophage pro-inflammatory gene expression and functions.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Atherosclerosis Profiling Reveals BHLHE40 as a Candidate Modulator of VSMC.Circulation research · 2026Article
- Hypoxia-responsive interaction between P-TEFb, BHLHE40, and Tim8-Tim13 regulates hypoxic gene transcription.Science advances · 2026Article
- Epidermal PPARγ Signaling as a Suppressor of Toll-like Receptor-Mediated Inflammation and Fibrosis: Relevance to Cutaneous Squamous Cell Carcinoma.International journal of molecular sciences · 2026Article
- Aligned cross-modal integration and regulatory heterogeneity characterization of single-cell multiomic data with deep contrastive learning.Genome medicine · 2026Article
- Endothelial mechanosensitive transcription factor BHLHE40 induced by Piezo1 suppresses endothelial ferroptosis and inflammation via SLC7A11.Cell death discovery · 2025Article
- IL-18 drives the Bhlhe40-mediated pathogenic Th17 cell response and exacerbates autoimmune disease progression.Cellular & molecular immunology · 2025Article
- Genomic crosstalk between carbachol, a muscarinic receptor agonist, and the long-acting βThe Journal of pharmacology and experimental therapeutics · 2025Article
- Exploring the molecular characteristics of inflammatory bowel disease from the perspective of hypoxia-related genes.Frontiers in pharmacology · 2025Article
- Article
- Single-cell RNA sequencing analysis of vestibular schwannoma reveals functionally distinct macrophage subsets.British journal of cancer · 2024Article
- BHLHE40 Regulates Myeloid Cell Polarization through IL-10-Dependent and -Independent Mechanisms.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Multi-omics analysis of human tendon adhesion reveals that ACKR1-regulated macrophage migration is involved in regeneration.Bone research · 2024Article
- DEC1 is involved in circadian rhythm disruption-exacerbated pulmonary fibrosis.Cell communication and signaling : CCS · 2024Article
- Single-Cell RNA Sequencing Reveals a Unique Fibroblastic Subset and Immune Disorder in Lichen Sclerosus Urethral Stricture.Journal of inflammation research · 2024Article
- Roles of pyroptosis and immune infiltration in aortic dissection.Frontiers in molecular biosciences · 2024Article
- Circadian gene signatures in the progression of obesity based on machine learning and Mendelian randomization analysis.Frontiers in nutrition · 2024Article
- Uncovering SPP1Journal of inflammation research · 2024Article
- Identification of Novel Diagnostic Biomarkers and Classification Patterns for Osteoarthritis by Analyzing a Specific Set of Genes Related to Inflammation.Inflammation · 2023Article
- Bhlhe40 limits early IL-10 production from CD4Infection and immunity · 2023Article
- Study on the Alleviating Effect and Potential Mechanism of Ethanolic Extract ofInternational journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Macrophages are the principal innate immune cells that populate all major organs and provide the first line of cellular defense against infections and/or injuries. The immediate and early-responding macrophages must mount a robust pro-inflammatory response to protect the host by eliminating deleterious agents. The effective pro-inflammatory macrophage response requires the activation of complex transcriptional programs that modulate the dynamic regulation of inflammatory and metabolic gene expression. Therefore, transcription factors that govern pro-inflammatory and metabolic gene expression play an essential role in shaping the macrophage inflammatory response. Herein, we identify the basic helix-loop-helix family member e40 (BHLHE40), as a critical transcription factor that promotes broad pro-inflammatory and glycolytic gene expression by elevating HIF1α levels in macrophages. Our in vivo studies revealed that myeloid-BHLHE40 deficiency significantly attenuates macrophage and neutrophil recruitment to the site of inflammation. Our integrated transcriptomics and gene set enrichment analysis (GSEA) studies show that BHLHE40 deficiency broadly curtails inflammatory signaling pathways, hypoxia response, and glycolytic gene expression in macrophages. Utilizing complementary gain- and loss-of-function studies, our analyses uncovered that BHLHE40 promotes LPS-induced HIF1α mRNA and protein expression in macrophages. More importantly, forced overexpression of oxygen stable form of HIF1α completely reversed attenuated pro-inflammatory and glycolytic gene expression in BHLHE40-deficient macrophages. Collectively, these results demonstrate that BHLHE40 promotes macrophage pro-inflammatory gene expression and functions by elevating HIF1α expression in macrophages.
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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 Socratic graph.