ArticleCells2020
GDF3 Protects Mice against Sepsis-Induced Cardiac Dysfunction and Mortality by Suppression of Macrophage Pro-Inflammatory Phenotype.
Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 77 citations in OpenAlex.
- Biomaterial-guided macrophage modulation: Therapeutic engineering of immune microenvironments.Trends in immunology · 2026Review
- Adipokine CTRP12 Alleviates Experimental Colitis by Participating in Modulating Mesenteric M2 Macrophage Polarization in IL-10 KO Mice.Digestive diseases and sciences · 2026Article
- Effect of premorbid beta-blockers on cardiac function and clinical outcomes in septic patients: a retrospective study.Journal of critical care medicine (Universitatea de Medicina si Farmacie din Targu-Mures) · 2026Article
- GDF3 promotes adipose tissue macrophage-mediated inflammation via altered chromatin accessibility during aging.Nature aging · 2026Article
- Progress on Potential Therapeutic Targets for Sepsis-Related Cardiac Dysfunction: From Basic Research to Clinical Translation.ImmunoTargets and therapy · 2026Review
- Modulation of Macrophage Polarization by Traditional Chinese Medicine in HFpEF: A Review of Mechanisms and Therapeutic Potentials.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Research progress on macrophages in cardiovascular diseases.Journal of cardiothoracic surgery · 2025Review
- Epigenetic regulatory mechanism of macrophage polarization in diabetic wound healing (Review).Molecular medicine reports · 2025Review
- NLRP3 Inflammasome Targeting Offers a Novel Therapeutic Paradigm for Sepsis-Induced Myocardial Injury.Drug design, development and therapy · 2025Review
- Probiotic bacteria-released extracellular vesicles enhance macrophage phagocytosis in polymicrobial sepsis by activating the FPR1/2 pathway.Molecular medicine (Cambridge, Mass.) · 2024Article
- Tumor‑associated macrophages activated in the tumor environment of hepatocellular carcinoma: Characterization and treatment (Review).International journal of oncology · 2024Review
- Mechanisms of the septic heart: From inflammatory response to myocardial edema.Journal of molecular and cellular cardiology · 2024Review
- Immune-response gene 1 deficiency aggravates inflammation-triggered cardiac dysfunction by inducing M1 macrophage polarization and aggravating Ly6CBiology direct · 2024Article
- Review
- Ceria nanozyme coordination with curcumin for treatment of sepsis-induced cardiac injury by inhibiting ferroptosis and inflammation.Journal of advanced research · 2024Article
- Article
- miR-29b-1-5p exacerbates myocardial injury induced by sepsis in a mouse model by targeting TERF2.Acta biochimica et biophysica Sinica · 2024Article
- Macrophage-enriched Sectm1a promotes efficient efferocytosis to attenuate ischemia/reperfusion-induced cardiac injury.JCI insight · 2024Article
- GDF3 Protects Mice against Sepsis-Induced Acute Lung Injury by Suppression of Macrophage Pyroptosis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Contribution of microglia/macrophage to the pathogenesis of TMEV infection in the central nervous system.Frontiers in microbiology · 2024Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
Macrophages are critical for regulation of inflammatory response during endotoxemia and septic shock. However, the mediators underlying their regulatory function remain obscure. Growth differentiation factor 3 (GDF3), a member of transforming growth factor beta (TGF-β) superfamily, has been implicated in inflammatory response. Nonetheless, the role of GDF3 in macrophage-regulated endotoxemia/sepsis is unknown. Here, we show that serum GDF3 levels in septic patients are elevated and strongly correlate with severity of sepsis and 28-day mortality. Interestingly, macrophages treated with recombinant GDF3 protein (rGDF3) exhibit greatly reduced production of pro-inflammatory cytokines, comparing to controls upon endotoxin challenge. Moreover, acute administration of rGDF3 to endotoxin-treated mice suppresses macrophage infiltration to the heart, attenuates systemic and cardiac inflammation with less pro-inflammatory macrophages (M1) and more anti-inflammatory macrophages (M2), as well as prolongs mouse survival. Mechanistically, GDF3 is able to activate Smad2/Smad3 phosphorylation, and consequently inhibits the expression of nod-like receptor protein-3 (NLRP3) in macrophages. Accordingly, blockade of Smad2/Smad3 phosphorylation with SB431542 significantly offsets rGDF3-mediated anti-inflammatory effects. Taken together, this study uncovers that GDF3, as a novel sepsis-associated factor, may have a dual role in the pathophysiology of sepsis. Acute administration of rGDF3 into endotoxic shock mice could increase survival outcome and improve cardiac function through anti-inflammatory response by suppression of M1 macrophage phenotype. However, constitutive high levels of GDF3 in human sepsis patients are associated with lethality, suggesting that GDF3 may promote macrophage polarization toward M2 phenotype which could lead to immunosuppression.
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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 OpenQuestion graph.