ArticlePloS one2014
Low-density lipoprotein receptor-related protein-1 mediates endocytic clearance of tissue inhibitor of metalloproteinases-1 and promotes its cytokine-like activities.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- TIMP1 Derived from Mesenchymal Stem Cells Promotes Bladder Cancer Progression by Regulating the Formation of VDIMs through the RAP1 Pathway.International journal of biological sciences · 2026Article
- TIMP-1 enhances Akt and BDNF signaling in neurons to reduce synaptic and cognitive deficits in 5xFAD mouse model of Alzheimer's disease.Acta neuropathologica communications · 2025Article
- Cold and hot fibrosis define clinically distinct cardiac pathologies.Cell systems · 2025Article
- Pan-cancer secreted proteome and skeletal muscle regulation: insight from a proteogenomic data-driven knowledge base.Functional & integrative genomics · 2025Review
- Human monocyte-derived macrophages shift subcellular metalloprotease activity depending on their activation state.iScience · 2024Article
- The Effect of Tissue Inhibitor of Metalloproteinases on Scar Formation after Spinal Cord Injury.Cells · 2024Review
- Novel insights into the multifaceted and tissue-specific roles of the endocytic receptor LRP1.The Journal of biological chemistry · 2024Review
- TIMP-1 is an activator of MHC-I expression in myeloid dendritic cells with implications for tumor immunogenicity.Genes and immunity · 2024Article
- Human platelet lysate: a potential therapeutic for intracerebral hemorrhage.Frontiers in neuroscience · 2024Review
- Prognostic significance of alpha-2-macrglobulin and low-density lipoprotein receptor-related protein-1 in various cancers.American journal of cancer research · 2024Article
- The invariant chain CD74 protein is a cell surface binding partner of TIMP-1 in breast cancer cells.Molecular oncology · 2023Article
- Article
- ADAM10-a "multitasker" in sepsis: focus on its posttranslational target.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Peripheral apoE4 enhances Alzheimer's pathology and impairs cognition by compromising cerebrovascular function.Nature neuroscience · 2022Article
- Unravelling the distinct biological functions and potential therapeutic applications of TIMP2 in cancer.Carcinogenesis · 2022Review
- Evaluating the Causal Effects of TIMP-3 on Ischaemic Stroke and Intracerebral Haemorrhage: A Mendelian Randomization Study.Frontiers in genetics · 2022Article
- Low-Density Lipoprotein Receptor-Related Protein 6 Cell Surface Availability Regulates Fuel Metabolism in Astrocytes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Article
- Tissue Inhibitor of Metalloprotease-1 (TIMP-1) Regulates Adipogenesis of Adipose-derived Stem Cells (ASCs) via the Wnt Signaling Pathway in an MMP-independent Manner.Current medical science · 2020Article
- High-Affinity Binding of LDL Receptor-Related Protein 1 to Matrix Metalloprotease 1 Requires Protease:Inhibitor Complex Formation.Biochemistry · 2020Article
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue inhibitor of metalloproteinases-1 (TIMP-1) regulates the extracellular matrix turnover by inhibiting the proteolytic activity of matrix metalloproteinases (MMPs). TIMP-1 also displays MMP-independent activities that influence the behavior of various cell types including neuronal plasticity, but the underlying molecular mechanisms remain mostly unknown. The trans-membrane receptor low-density lipoprotein receptor-related protein-1 (LRP-1) consists of a large extracellular chain with distinct ligand-binding domains that interact with numerous ligands including TIMP-2 and TIMP-3 and a short transmembrane chain with intracellular motifs that allow endocytosis and confer signaling properties to LRP-1. We addressed TIMP-1 interaction with recombinant ligand-binding domains of LRP-1 expressed by CHO cells for endocytosis study, or linked onto sensor chips for surface plasmon resonance analysis. Primary cortical neurons bound and internalized endogenous TIMP-1 through a mechanism mediated by LRP-1. This resulted in inhibition of neurite outgrowth and increased growth cone volume. Using a mutated inactive TIMP-1 variant we showed that TIMP-1 effect on neurone morphology was independent of its MMP inhibitory activity. We conclude that TIMP-1 is a new ligand of LRP-1 and we highlight a new example of its MMP-independent, cytokine-like functions.
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