Evidence map›Paper›PMID 36275631›Full record

ArticleFrontiers in molecular biosciences2022

Noncovalent hyaluronan crosslinking by TSG-6: Modulation by heparin, heparan sulfate, and PRG4.

Yun Jin Ashley Sin, Rebecca MacLeod, Adam P Tanguay, Andrew Wang, Olivia Braender-Carr, Teraesa M Vitelli, Gregory D Jay, Tannin A Schmidt, Mary K Cowman

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in molecular biosciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.6field-weighted citation impact, top 39% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
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

9 authors at 4 institutions in 1 country.

Yun Jin Ashley SinDepartment of Biomedical Engineering, Tandon School of Engineering, New York University, New York, NY, United States.
Rebecca MacLeodDepartment of Biomedical Engineering, Tandon School of Engineering, New York University, New York, NY, United States.
Adam P TanguayDepartment of Biomedical Engineering, School of Dental Medicine, UConn Health, Farmington, CT, United States.
Andrew WangNew York Medical College, Valhalla, NY, United States.
Olivia Braender-CarrDepartment of Biomedical Engineering, Tandon School of Engineering, New York University, New York, NY, United States.
Teraesa M VitelliDepartment of Biomedical Engineering, Tandon School of Engineering, New York University, New York, NY, United States.
Gregory D JayDepartment of Emergency Medicine, Warren Alpert Medical School and School of Engineering, Brown University, Providence, RI, United States.
Tannin A SchmidtDepartment of Biomedical Engineering, School of Dental Medicine, UConn Health, Farmington, CT, United States.
Mary K CowmanDepartment of Biomedical Engineering, Tandon School of Engineering, New York University, New York, NY, United States.
New York University · USUConn Health · USBrown University · USNew York Medical College · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The size, conformation, and organization of the glycosaminoglycan hyaluronan (HA) affect its interactions with soluble and cell surface-bound proteins. HA that is induced to form stable networks has unique biological properties relative to unmodified soluble HA. AlphaLISA assay technology offers a facile and general experimental approach to assay protein-mediated networking of HA in solution. Connections formed between two end-biotinylated 50 kDa HA (bHA) chains can be detected by signal arising from streptavidin-coated donor and acceptor beads being brought into close proximity when the bHA chains are bridged by proteins. We observed that incubation of bHA with the protein TSG-6 (tumor necrosis factor alpha stimulated gene/protein 6, TNFAIP/TSG-6) leads to dimerization or higher order multimerization of HA chains in solution. We compared two different heparin (HP) samples and two heparan sulfate (HS) samples for the ability to disrupt HA crosslinking by TSG-6. Both HP samples had approximately three sulfates per disaccharide, and both were effective in inhibiting HA crosslinking by TSG-6. HS with a relatively high degree of sulfation (1.75 per disaccharide) also inhibited TSG-6 mediated HA networking, while HS with a lower degree of sulfation (0.75 per disaccharide) was less effective. We further identified Proteoglycan 4 (PRG4, lubricin) as a TSG-6 ligand, and found it to inhibit TSG-6-mediated HA crosslinking. The effects of HP, HS, and PRG4 on HA crosslinking by TSG-6 were shown to be due to HP/HS/PRG4 inhibition of HA binding to the Link domain of TSG-6. Using the AlphaLISA platform, we also tested other HA-binding proteins for ability to create HA networks. The G1 domain of versican (VG1) effectively networked bHA in solution but required a higher concentration than TSG-6. Cartilage link protein (HAPLN1) and the HA binding protein segment of aggrecan (HABP, G1-IGD-G2) showed only low and variable magnitude HA networking effects. This study unambiguously demonstrates HA crosslinking in solution by TSG-6 and VG1 proteins, and establishes PRG4, HP and highly sulfated HS as modulators of TSG-6 mediated HA crosslinking.

Indexed as

glycosaminoglycanheparan sulfateheparinhyaluronanlubricinPRG4TSG-6versican

Identifiers

PMID36275631
PMCPMC9579337
OpenAlexW4301393953

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.