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Record W2956079787 · doi:10.1096/fba.2019-00011

Podocyte GSK3α is important for autophagy and its loss detrimental for glomerular function

2019· article· en· W2956079787 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueFASEB BioAdvances · 2019
Typearticle
Languageen
FieldMedicine
TopicRenal Diseases and Glomerulopathies
Canadian institutionsSinai Health SystemLunenfeld-Tanenbaum Research InstituteUniversity of Toronto
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesCanadian Institutes of Health ResearchEuropean CommissionNational Institutes of HealthKidney Research UKMedical Research CouncilEuropean Federation of Pharmaceutical Industries and AssociationsInnovative Medicines InitiativeHorizon 2020 Framework ProgrammeJuvenile Diabetes Research Foundation International
KeywordsPodocyteGSK-3Cell biologyAlbuminuriaDiabetic nephropathyAutophagyGene isoformBiologyPhosphorylationCancer researchChemistryEndocrinologyRenal functionKidneyBiochemistryProteinuria

Abstract

fetched live from OpenAlex

Abstract Podocytes are key cells in maintaining the integrity of the glomerular filtration barrier and preventing albuminuria. Glycogen synthase kinase 3 (GSK3) is a multi‐functional serine/threonine kinase existing as two distinct but related isoforms (α and β). In the podocyte it has previously been reported that inhibition of the β isoform is beneficial in attenuating a variety of glomerular disease models but loss of both isoforms is catastrophic. However, it is not known what the role of GSK3α is in these cells. We now show that GSK3α is present and dynamically modulated in podocytes. When GSK3α is transgenically knocked down specifically in the podocytes of mice it causes mild but significant albuminuria by 6 weeks of life. Its loss also does not protect in models of diabetic or Adriamycin‐induced nephropathy. In vitro deletion of podocyte GSK3α causes cell death and impaired autophagic flux suggesting it is important for this key cellular process. Collectively this work shows that GSK3α is important for podocyte health and that augmenting its function may be beneficial in treating glomerular disease.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.314
Threshold uncertainty score0.548

Codex and Gemma teacher scores by category

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)0.0000.000

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 head0.011
GPT teacher head0.281
Teacher spread0.269 · 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