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Record W2320024442 · doi:10.14288/1.0067924

Metalloproteinase cleavage of versican at the fibroblast cell surface

2009· article· en· W2320024442 on OpenAlexaff
Sean B Maurice

Bibliographic record

VenuecIRcle (University of British Columbia) · 2009
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtease and Inhibitor Mechanisms
Canadian institutionsUniversity of British Columbia
Fundersnot available
KeywordsVersicanMetalloproteinaseCleavage (geology)FibroblastCell biologyCellChemistryMatrix metalloproteinaseBiochemistryBiologyExtracellular matrixProteoglycanIn vitro

Abstract

fetched live from OpenAlex

Versican is a large aggregating proteoglycan expressed in the pericellular matrix of fibroblast cells. It is highly expressed during development and remodeling. The regulated synthesis and degradation of versican are associated with physiological remodeling. Versican is expressed in fibroproliferative lesions of human pulmonary fibrosis and atherosclerosis. Stromal expression of versican is associated with many forms of cancer and may be predictive of poor prognosis. Abnormal persistence of the versican-rich matrix may contribute to fibroproliferative and oncogenic processes. The process of versican degradation is not understood, but as versican is a pericellular molecule, physiological degradation likely involves cell surface-associated proteolysis. As such, the overarching hypothesis for this work is that regulated versican turnover involves the cell surface-associated metalloproteinases ADAMTS-2, MMP-2 and MT1-MMP, that are expressed in versican-rich remodeling lesions. ADAMTS-2 is a procollagen N-propeptidase involved in collagen fibrillogenesis. As procollagen is synthesized in a versican-rich matrix, it was hypothesized that ADAMTS- 2 might bind and process versican. MMP-2 and MT1-MMP in complex with TIMP-2, are activated at the cell surface during wound healing, pulmonary fibrosis and cancer. Versican was purified from human fetal lung fibroblast cultures for in vitro proteolysis experiments. The purified versican preparation was characterized by electrophoresis, chromatography, spectrophotometry and mass spectrometry. ADAMTS-2 and versican localization in normal and fibrotic human lungs were investigated. ADAMTS-2 was shown to co-purify with versican from human fetal lung fibroblasts. Bovine ADAMTS-2 was purified from fetal calf skin and shown to cleave purified human versican. The plant lectin concanavalin-A (ConA) induces a matrix degradative phenotype and is used here to investigate the process of versican degradation relative to apoptotic iii events in human fetal lung fibroblast cultures. Con-A induced increased expression of MMP-2 and MT1-MMP in human fetal lung fibroblasts and a concomitant loss of versican from the matrix. Microarray analysis was used to investigate expression of possible versican-degrading enzymes and their inhibitors, expressed in response to ConA. Recombinant MMP-2 and MT1-MMP were shown to process purified versican in vitro. This work expands upon the body of knowledge of versican turnover and should help in the search for therapeutic avenues to treat fibroproliferative and oncogenic processes.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.004
GPT teacher head0.156
Teacher spread0.152 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2009
Admission routes1
Has abstractyes

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