uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Hyaluronan Synthesis Is Inhibited by Adenosine Monophosphate-activated Protein Kinase through the Regulation of HAS2 Activity in Human Aortic Smooth Muscle Cells
Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Universita` degli Studi dell’Insubria, Via J. H. Dunant 5, 21100 Varese, Italy.
Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Universita` degli Studi dell’Insubria, Via J. H. Dunant 5, 21100 Varese, Italy.
Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Universita` degli Studi dell’Insubria, Via J. H. Dunant 5, 21100 Varese, Italy.
Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Universita` degli Studi dell’Insubria, Via J. H. Dunant 5, 21100 Varese, Italy.
Show others and affiliations
2011 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 286, no 10, 7917-7924 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2011. Vol. 286, no 10, 7917-7924 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-149803DOI: 10.1074/jbc.M110.193656ISI: 000288013300022PubMedID: 21228273OAI: oai:DiVA.org:uu-149803DiVA: diva2:405725
Available from: 2011-03-23 Created: 2011-03-23 Last updated: 2017-12-11Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Ludwig Institute for Cancer Research
In the same journal
Journal of Biological Chemistry
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 399 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf