ArticleClinical and translational medicine2024
Macrophage OTUD1-CARD9 axis drives isoproterenol-induced inflammatory heart remodelling.
Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Targeting the OTU family: a core therapeutic strategy for reshaping the immunosuppressive microenvironment and reversing drug resistance in HCC by coordinating the autophagy-ferroptosis balance.Cell death discovery · 2026Review
- The role of OTUD1-mediated deubiquitination in disease pathogenesis: from molecular mechanisms to clinical translation.Frontiers in immunology · 2026Review
- YOD1 mediates isoproterenol-induced cardiac remodeling by deubiquitinating PKM2 and reducing PKM2 tetramerization in cardiomyocytes.Acta pharmacologica Sinica · 2025Article
- Inflammation-Related Factors S100A9 and TLR2 in Cardiomyocyte Hypertrophy.Current medical science · 2025Article
- Cardiomyocyte-derived YOD1 promotes pathological cardiac hypertrophy by deubiquitinating and stabilizing STAT3.Science advances · 2025Article
- OTUD1 exacerbates sepsis-associated encephalopathy by promoting HK2 mitochondrial release to drive microglia pyroptosis.Journal of neuroinflammation · 2025Article
- Understanding of the characteristics of fibroblasts in ischemic cardiomyopathy using single-nucleus RNA sequencing.Scientific reports · 2025Article
- Scaffold Proteins in Fibrotic Diseases of Visceral Organs.Biomolecules · 2025Review
- The Ubiquitin-Proteasome System: A Key Regulatory Hub in Myocarditis Leading to Dilated Cardiomyopathy.Journal of inflammation research · 2025Review
- Macrophages in ventricular remodeling and heart failure: orchestrators of inflammation and repair.Frontiers in immunology · 2025Review
- Exacerbation by knocking-out metallothionein gene of obesity-induced cardiac remodeling is associated with the activation of CARD9 signaling.International journal of biological sciences · 2025Article
- OTUD1 inhibits osteoclast differentiation and osteoclastic bone loss through deubiquitinating and stabilizing PRDX1.Theranostics · 2025Article
- Macrophage OTUD1-CARD9 axis drives isoproterenol-induced inflammatory heart remodelling.Clinical and translational medicine · 2024Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
backgroundChronic inflammation contributes to the progression of isoproterenol (ISO)-induced heart failure (HF). Caspase-associated recruitment domain (CARD) families are crucial proteins for initiation of inflammation in innate immunity. Nonetheless, the relevance of CARDs in ISO-driven cardiac remodelling is little explored.
methodsThis study utilized Card9
resultsHere, we demonstrated that CARD9 was substantially upregulated in murine hearts infused with ISO. Either whole-body CARD9 knockout or myeloid-specific CARD9 deletion inhibited ISO-driven murine cardiac inflammation, remodelling and dysfunction. CARD9 deficiency in macrophages prevented ISO-induced inflammation and alleviated remodelling changes in cardiomyocytes and fibroblasts. Mechanistically, we found that ISO enhances the activity of CARD9 by upregulating ovarian tumour deubiquitinase 1 (OTUD1) in macrophages. We further demonstrated that OTUD1 directly binds to the CARD9 and then removes the K33-linked ubiquitin from CARD9 to promote the assembly of the CARD9-BCL10-MALT1 (CBM) complex, without affecting CARD9 stability. The ISO-activated CBM complex results in NF-κB activation and macrophage-based inflammatory gene overproduction, which then enhances cardiomyocyte hypertrophy and fibroblast fibrosis, respectively. Myeloid-specific OTUD1 deletion also attenuated ISO-induced murine cardiac inflammation and remodelling.
conclusionsThese results suggested that the OTUD1-CARD9 axis is a new pro-inflammatory signal in ISO-challenged macrophages and targeting this axis has a protective effect against ISO-induced HF. KEY POINTS: Macrophage CARD9 was elevated in heart tissues of mice under chronic ISO administration. Either whole-body CARD9 knockout or myeloid-specific CARD9 deficiency protected mice from ISO-induced inflammatory heart remodeling. ISO promoted the assembly of CBM complex and then activated NF-κB signaling in macrophages through OTUD1-mediated deubiquitinating modification. OTUD1 deletion in myeloid cells protected hearts from ISO-induced injuries in mice.
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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 Socratic graph.