ArticleThe Journal of biological chemistry2019
C-terminal proteolysis of the collagen VI α3 chain by BMP-1 and proprotein convertase(s) releases endotrophin in fragments of different sizes.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 58 citations in OpenAlex.
- Characterization of a novel assay for full-length endotrophin in heart failure with preserved ejection fraction.Scientific reports · 2026Article
- Targeting COL6A3-C5 with nigericin suppresses endotrophin formation and enhances insulin sensitivity in obesity.Experimental & molecular medicine · 2026Article
- COX-2/PGE₂ signaling drives Toxocara canis-induced lung pathology by enhancing plasminogen activator activity and collagen VI degradation.Scientific reports · 2025Article
- ETP-specific-knockout mice reveal endotrophin as a key regulator of kidney fibrosis in ischemia-reperfusion injury models.Experimental & molecular medicine · 2025Article
- Urinary endotrophin as a biomarker for T cell-mediated rejection-associated fibrogenesis in kidney transplant recipients.Clinical kidney journal · 2025Article
- The Role ofCancers · 2025Review
- Collagen VI microfibril structure reveals mechanism for molecular assembly and clustering of inherited pathogenic mutations.Nature communications · 2025Article
- Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease.Nature genetics · 2025Article
- Biomarkers in ANCA associated vasculitis: clinical utility, pitfalls and their role in the outcomes assessment.Frontiers in immunology · 2025Review
- Endotrophin, a Key Marker and Driver for Fibroinflammatory Disease.Endocrine reviews · 2024Review
- The coordinated activities of collagen VI and XII in maintenance of tissue structure, function and repair: evidence for a physical interaction.Frontiers in molecular biosciences · 2024Article
- Combination Therapy of RAS Inhibition and SGLT2 Inhibitors Decreases Levels of Endotrophin in Persons with Type 2 Diabetes.Biomedicines · 2023Article
- The UCMD-CausingHuman mutation · 2023Article
- Article
- Endotrophin, a Collagen VI Formation-Derived Peptide, in Heart Failure.NEJM evidence · 2022Article
- Endotrophin, a collagen type VI-derived matrikine, reflects the degree of renal fibrosis in patients with IgA nephropathy and in patients with ANCA-associated vasculitis.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2022Article
- Collagen VI Regulates Motor Circuit Plasticity and Motor Performance by Cannabinoid Modulation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Procollagen C-proteinase enhancer-1 (PCPE-1), a potential biomarker and therapeutic target for fibrosis.Matrix biology plus · 2021Article
- Activin-A Induces Early Differential Gene Expression Exclusively in Periodontal Ligament Fibroblasts fromBiomedicines · 2021Article
- Collagen VI Muscle Disorders: Mutation Types, Pathogenic Mechanisms and Approaches to Therapy.Advances in experimental medicine and biology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The assembly of collagen VI microfibrils is a multistep process in which proteolytic processing within the C-terminal globular region of the collagen VI α3 chain plays a major role. However, the mechanisms involved remain elusive. Moreover, C5, the short and most C-terminal domain of the α3 chain, recently has been proposed to be released as an adipokine that enhances tumor progression, fibrosis, inflammation, and insulin resistance and has been named "endotrophin." Serum endotrophin could be a useful biomarker to monitor the progression of such disorders as chronic obstructive pulmonary disease, systemic sclerosis, and kidney diseases. Here, using biochemical and isotopic MS-based analyses, we found that the extracellular metalloproteinase bone morphogenetic protein 1 (BMP-1) is involved in endotrophin release and determined the exact BMP-1 cleavage site. Moreover, we provide evidence that several endotrophin-containing fragments are present in various tissues and body fluids. Among these, a large C2-C5 fragment, which contained endotrophin, was released by furin-like proprotein convertase cleavage. By using immunofluorescence microscopy and EM, we also demonstrate that these proteolytic maturations occur after secretion of collagen VI tetramers and during microfibril assembly. Differential localization of N- and C-terminal regions of the collagen VI α3 chain revealed that cleavage products are deposited in tissue and cell cultures. The detailed information on the processing of the collagen VI α3 chain reported here provides a basis for unraveling the function of endotrophin (C5) and larger endotrophin-containing fragments and for refining their use as biomarkers of disease progression.
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Registered trials
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