Evidence map›Paper›PMID 22887999›Full record

ArticleThe Journal of biological chemistry2012

Role of UDP-N-acetylglucosamine (GlcNAc) and O-GlcNAcylation of hyaluronan synthase 2 in the control of chondroitin sulfate and hyaluronan synthesis.

Davide Vigetti, Sara Deleonibus, Paola Moretto, Eugenia Karousou, Manuela Viola, Barbara Bartolini, Vincent C Hascall, Markku Tammi, Giancarlo De Luca, Alberto Passi

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

77 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Hyaluronan in cardiac disease: implications for the extracellular matrix beyond collagen.American journal of physiology. Heart and circulatory physiology · 2026
    Review
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  17. The O-GlcNAc dichotomy: when does adaptation become pathological?Clinical science (London, England : 1979) · 2023
    Review
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  20. Cells · 2023
    Review

17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 3 countries.

Davide VigettiDipartimento di Scienze Chirurgiche e Morfologiche, Università degli Studi dell'Insubria, via J. H. Dunant 5, 21100 Varese, Italy.
Sara DeleonibusDipartimento di Scienze Chirurgiche e Morfologiche, Università degli Studi dell'Insubria, via J. H. Dunant 5, 21100 Varese, Italy.
Paola MorettoDipartimento di Scienze Chirurgiche e Morfologiche, Università degli Studi dell'Insubria, via J. H. Dunant 5, 21100 Varese, Italy.
Eugenia KarousouDipartimento di Scienze Chirurgiche e Morfologiche, Università degli Studi dell'Insubria, via J. H. Dunant 5, 21100 Varese, Italy.
Manuela ViolaDipartimento di Scienze Chirurgiche e Morfologiche, Università degli Studi dell'Insubria, via J. H. Dunant 5, 21100 Varese, Italy.
Barbara BartoliniDipartimento di Scienze Chirurgiche e Morfologiche, Università degli Studi dell'Insubria, via J. H. Dunant 5, 21100 Varese, Italy.
Vincent C HascallBiomedical Engineering ND20, The Cleveland Clinic, Cleveland, Ohio 44195.
Markku TammiInstitute of Biomedicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
Giancarlo De LucaDipartimento di Scienze Chirurgiche e Morfologiche, Università degli Studi dell'Insubria, via J. H. Dunant 5, 21100 Varese, Italy.
Alberto PassiDipartimento di Scienze Chirurgiche e Morfologiche, Università degli Studi dell'Insubria, via J. H. Dunant 5, 21100 Varese, Italy. Electronic address: alberto.passi@uninsubria.it.
University of Insubria · ITCleveland Clinic · USUniversity of Eastern Finland · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hyaluronan (HA) is a glycosaminoglycan present in most tissue microenvironments that can modulate many cell behaviors, including proliferation, migration, and adhesive proprieties. In contrast with other glycosaminoglycans, which are synthesized in the Golgi, HA is synthesized at the plasma membrane by one or more of the three HA synthases (HAS1-3), which use cytoplasmic UDP-glucuronic acid and UDP-N-acetylglucosamine as substrates. Previous studies revealed the importance of UDP-sugars for regulating HA synthesis. Therefore, we analyzed the effect of UDP-GlcNAc availability and protein glycosylation with O-linked N-acetylglucosamine (O-GlcNAcylation) on HA and chondroitin sulfate synthesis in primary human aortic smooth muscle cells. Glucosamine treatment, which increases UDP-GlcNAc availability and protein O-GlcNAcylation, increased synthesis of both HA and chondroitin sulfate. However, increasing O-GlcNAcylation by stimulation with O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate without a concomitant increase of UDP-GlcNAc increased only HA synthesis. We found that HAS2, the main synthase in aortic smooth muscle cells, can be O-GlcNAcylated on serine 221, which strongly increased its activity and its stability (t(½) >5 h versus ∼17 min without O-GlcNAcylation). S221A mutation prevented HAS2 O-GlcNAcylation, which maintained the rapid turnover rate even in the presence of GlcN and increased UDP-GlcNAc. These findings could explain the elevated matrix HA observed in diabetic vessels that, in turn, could mediate cell dedifferentiation processes critical in vascular pathologies.

Indexed as

Amino Acid SubstitutionAortaCell LineChondroitin SulfatesDiabetic AngiopathiesGlucuronosyltransferaseGlycosylationHumansHyaluronan SynthasesHyaluronic AcidMuscle ProteinsMuscle, Smooth, VascularMutation, MissenseUridine Diphosphate N-AcetylglucosamineChondroitin SulfatesGlucuronosyltransferaseHAS1 protein, humanHAS2 protein, humanHAS3 protein, humanHyaluronan SynthasesHyaluronic AcidMuscle ProteinsUridine Diphosphate N-Acetylglucosamine

Identifiers

PMID22887999
PMCPMC3471761
OpenAlexW2064039937

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.