Evidence map›Paper›PMID 39401868›Full record

ArticleNephrology (Carlton, Vic.)2024

POU2F2 activates the Akt/mTOR signalling pathway and enhances B lymphocyte function during diabetic kidney disease by promoting PIK3CD transcription.

Xiaoxia Li, Shukun Cao, Xiaolin Zi, Haiqiao Yu, Chunmei Mao

Abstract read
In one paragraph

Article in Nephrology (Carlton, Vic.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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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

1 citing paper in PubMed.

  1. The association study betweenAdvances in ophthalmology practice and research
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4 · The record

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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

5 authors.

Xiaoxia LiDepartment of Medical Laboratory, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
Shukun CaoSchool of Medical Laboratory and Technology, Harbin Medical University, Daqing, Heilongjiang, People's Republic of China.
Xiaolin ZiDepartment of Oncology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
Haiqiao YuDepartment of Endocrinology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
Chunmei MaoDepartment of Endocrinology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.ORCID https://orcid.org/0009-0000-7579-9900

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPhosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD) is the predominant isoform of the catalytic subunit of PI3K in lymphocytes. Based on comprehensive bioinformatics, this study explores the functions of PIK3CD in diabetic kidney disease (DKD) progression in mice and B lymphocyte activity.

methodsNon-obese diabetic (NOD) mice that spontaneously develop DKD were applied as animal models. Lentiviral vector-mediated PIK3CD silencing was introduced in mice, followed by histological staining and biomarker assessments to evaluate DKD-associated symptoms. The activity of the Akt/mTOR signalling pathway was determined by western blot analysis. Following bioinformatics analyses, the interaction between POU class 2 homeobox 2 (POU2F2) and PIK3CD in B lymphocytes was determined by chromatin immunoprecipitation and luciferase reporter assays. Their functions in B cell function were identified by MTT, flow cytometry and IgG deposition assessment.

resultsPIK3CD was found to be highly expressed in the kidney of DKD mice. Knockdown of PIK3CD inactivated the Akt/mTOR signalling, thus ameliorating tissue injury and fibrosis, enhancing the expression of AQP1 and decreasing urinary NGAL contents, UACR, BUN and β-NAG/creatinine ratio. These effects were negated by the Akt-specific activator SC79. POU2F2 was found to promote PIK3CD transcription by binding to its promoter, thus activating the Akt/mTOR pathway. Knockdown of POU2F2 suppressed B cell proliferation in vitro and decreased B cell population and IgG deposition in the mouse kidney. However, these trends were reversed upon additional PIK3CD overexpression.

conclusionThis study demonstrates that POU2F2 mediates PIK3CD-dependent Akt/mTOR signalling activation, thus enhancing B lymphocyte function and promoting DKD progression.

Indexed as

B-LymphocytesDiabetic NephropathiesProto-Oncogene Proteins c-aktSignal TransductionTOR Serine-Threonine KinasesAnimalsCell ProliferationClass I Phosphatidylinositol 3-KinasesDisease Models, AnimalKidneyMiceMice, Inbred NODOctamer Transcription Factor-2Transcription, GeneticClass I Phosphatidylinositol 3-KinasesmTOR protein, mouseOctamer Transcription Factor-2Proto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesAkt/mTOR signalling pathwayB lymphocytediabetic kidney diseasePIK3CDPOU2F2

Identifiers

PMID39401868
PMCPMC13546949

What Socratic holds

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Registered trials

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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 Socratic graph.