ArticleThe Journal of biological chemistry2011
Hyaluronan synthesis is inhibited by adenosine monophosphate-activated protein kinase through the regulation of HAS2 activity in human aortic smooth muscle cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 118 citations in OpenAlex.
- Metformin inhibits PDGFβ signaling to suppress hyaluronan and cytokine production in thyroid eye disease.Experimental eye research · 2026Article
- The myofascial rheostat: hyaluronan molecular weight dynamics and purinergic signalling as a physiological feedback system.Frontiers in physiology · 2026Review
- Understanding Fascial Tissue on the Molecular Level-How Its Unique Properties Enable Adaptation or Dysfunction.International journal of molecular sciences · 2025Review
- TargetingbioRxiv : the preprint server for biology · 2025Article
- Myosin-actin pattern links matrix stiffness to GFAT2-hyaluronan metabolism.Materials today. Bio · 2025Article
- The roles of hyaluronan in kidney development, physiology and disease.Nature reviews. Nephrology · 2024Review
- Hyaluronic acid metabolism and chemotherapy resistance: recent advances and therapeutic potential.Molecular oncology · 2024Review
- Effects of Hyaluronan on Breast Cancer Aggressiveness.Cancers · 2023Review
- Hyaluronan in the Cancer Cells Microenvironment.Cancers · 2023Review
- Metformin relaxes rat thoracic aorta via nitric oxide, AMPK, potassium channels, and PKC.Iranian journal of basic medical sciences · 2023Article
- Aggrecan and Hyaluronan: The Infamous Cartilage Polyelectrolytes - Then and Now.Advances in experimental medicine and biology · 2023Article
- Glucocorticoids Directly Affect Hyaluronan Production of Orbital Fibroblasts; A Potential Pleiotropic Effect in Graves' Orbitopathy.Molecules (Basel, Switzerland) · 2022Article
- Identification of a Small Molecule Inhibitor of Hyaluronan Synthesis, DDIT, Targeting Breast Cancer Cells.Cancers · 2022Article
- Inheritance of Monogenic Hereditary Skin Disease and Related Canine Breeds.Veterinary sciences · 2022Review
- Effect of SARS-CoV-2 infection on asthma patients.Frontiers in medicine · 2022Article
- Comorbidity-associated glutamine deficiency is a predisposition to severe COVID-19.Cell death and differentiation · 2021Review
- The role of the multifaceted long non-coding RNAs: A nuclear-cytosolic interplay to regulate hyaluronan metabolism.Matrix biology plus · 2021Article
- Inflammation, Extracellular Matrix Remodeling, and Proteostasis in Tumor Microenvironment.International journal of molecular sciences · 2021Review
- The Secreted Protein C10orf118 Is a New Regulator of Hyaluronan Synthesis Involved in Tumour-Stroma Cross-Talk.Cancers · 2021Article
- Cell Energy Metabolism and Hyaluronan Synthesis.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyaluronan (HA) is an extracellular matrix glycosaminoglycan (GAG) involved in cell motility, proliferation, tissue remodeling, development, differentiation, inflammation, tumor progression, and invasion and controls vessel thickening in cardiovascular diseases. Therefore, the control of HA synthesis could permit the fine-tuning of cell behavior, but the mechanisms that regulate HA synthesis are largely unknown. Recent studies suggest that the availability of the nucleotide-sugar precursors has a critical role. Because the formation of UDP-sugars is a highly energetically demanding process, we have analyzed whether the energy status of the cell could control GAG production. AMP-activated protein kinase (AMPK) is the main ATP/AMP sensor of mammalian cells, and we mimicked an energy stress by treating human aortic smooth muscle cells (AoSMCs) with the AMPK activators 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside and metformin. Under these conditions, HA synthesis, but not that of the other GAGs, was greatly reduced. We confirmed the inhibitory effect of AMPK using a specific inhibitor and knock-out cell lines. We found that AMPK phosphorylated Thr-110 of human HAS2, which inhibits its enzymatic activity. In contrast, the other two HAS isoenzymes (HAS1 and HAS3) were not modified by the kinase. The reduction of HA decreased the ability of AoSMCs to proliferate, migrate, and recruit immune cells, thereby reducing the pro-atherosclerotic AoSMC phenotype. Interestingly, such effects were not recovered by treatment with exogenous HA, suggesting that AMPK can block the pro-atherosclerotic signals driven by HA by interaction with its receptors.
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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 OpenQuestion graph.