ArticleImmunity, inflammation and disease2023
TFRC in cardiomyocytes promotes macrophage infiltration and activation during the process of heart failure through regulating Ccl2 expression mediated by hypoxia inducible factor-1α.
Article in Immunity, inflammation and disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 10 citations in OpenAlex.
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- Necroptosis induced by MLKL overexpression in liver triggers cellular senescence and leads to chronic inflammation and fibrosis.GeroScience · 2026Article
- Hepatic Hypoxia-Inducible Factor 1α Mediates Ferroptosis via Transferrin Receptor 1 in Acute Liver Injury.Antioxidants (Basel, Switzerland) · 2026Article
- Mechanistic Investigation of Salidroside Modulates Iron Overload to Mitigate Radiation-Induced Heart Disease.Cardiovascular therapeutics · 2026Article
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- Bioinformatics analysis and experimental validation of ferroptosis genes in heart failure and atrial fibrillation.Frontiers in genetics · 2025Article
- Hypoxia-inducible factor-1α can reverse the Adriamycin resistance of breast cancer adjuvant chemotherapy by upregulating transferrin receptor and activating ferroptosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Identification of TFRC as a biomarker for pulmonary arterial hypertension based on bioinformatics and experimental verification.Respiratory research · 2024Article
- Article
- Targeting Macrophage Phenotype for Treating Heart Failure: A New Approach.Drug design, development and therapy · 2024Review
- TFRC in cardiomyocytes promotes macrophage infiltration and activation during the process of heart failure through regulating Ccl2 expression mediated by hypoxia inducible factor-1α.Immunity, inflammation and disease · 2023Article
- Identification CCL2,CXCR2,S100A9 of the immune-related gene markers and immune infiltration characteristics of inflammatory bowel disease and heart failure via bioinformatics analysis and machine learning.Frontiers in cardiovascular medicine · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCardiac hypertrophy is an initiating link to Heart failure (HF) which still seriously endangers human health. Transferrin receptor (TFRC), which promotes iron uptake through the transferrin cycle, is essential for cardiac function. However, whether TFRC is involved in the process of pathological cardiac hypertrophy is not clear.
methodsTransverse aortic constriction (TAC) mouse model and mice primary cardiomyocytes treated with isoproterenol (ISO) or phenylephrine (PHE) were used to mimic cardiac hypertrophy in vivo and in vitro. Single cell RNA sequence data from heart tissues of TAC-model mice was obtained from the Gene Expression Omnibus (GEO) database, and was analyzed with R package Seurat. TFRC expression and macrophage infiltration in the heart tissue were tested by immunofluorescent staining. Macrophage polarization was detected by Flow Cytometry. TFRC expressions were detected by qRT-PCR, Western blot, and ELISA.
resultsTFRC expression is increased in the pathological cardiac hypertrophy of mice model and positively associated with macrophage infiltration. Furthermore, TFRC in cardiomyocytes recruits and activates macrophages by secreting C-C motif ligand 2 (Ccl2) in the mice heart tissue with TAC surgery or in the primary cardiomyocytes stimulated with ISO or PHE to induce myocardial hypertrophy in vitro. Moreover, we find that TFRC promotes Ccl2 expression in cardiomyocytes via regulating signal transducer and activator of transcription 3 (STAT3). In addition, we find that increased TFRC expression in the HF tissue is regulated by hypoxia-inducible factor-1α (HIF-1α).
conclusionThis in-depth study shows that TFRC in cardiomyocytes promotes HF development through inducing macrophage infiltration and activation via the STAT3-Ccl2 signaling, and TFRC expression in cardiomyocytes is regulated by HIF-1α during HF. This study first uncovers the role of TFRC in cardiomyocytes on macrophage infiltration and activation during HF.
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