Evidence map›Paper›PMID 34828301›Full record

ArticleGenes2021

Cathepsin C Regulates Cytokine-Induced Apoptosis in β-Cell Model Systems.

Tina Fløyel, Caroline Frørup, Joachim Størling, Flemming Pociot

Open access · goldAbstract read
In one paragraph

Article in Genes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

7 citing papers in PubMed, 25 citations in OpenAlex.

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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

4 authors at 2 institutions in 1 country.

Tina FløyelTranslational Type 1 Diabetes Research, Clinical Research, Steno Diabetes Center Copenhagen, 2820 Gentofte, Denmark.ORCID 0000-0003-4746-2627
Caroline FrørupTranslational Type 1 Diabetes Research, Clinical Research, Steno Diabetes Center Copenhagen, 2820 Gentofte, Denmark.ORCID 0000-0002-5675-8748
Joachim StørlingTranslational Type 1 Diabetes Research, Clinical Research, Steno Diabetes Center Copenhagen, 2820 Gentofte, Denmark.ORCID 0000-0002-7529-4264
Flemming PociotTranslational Type 1 Diabetes Research, Clinical Research, Steno Diabetes Center Copenhagen, 2820 Gentofte, Denmark.ORCID 0000-0003-3274-5448
Steno Diabetes Centers · DKUniversity of Copenhagen · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Emerging evidence suggests that several of the lysosomal cathepsin proteases are genetically associated with type 1 diabetes (T1D) and participate in immune-mediated destruction of the pancreatic β cells. We previously reported that the T1D candidate gene cathepsin H is downregulated by pro-inflammatory cytokines in human pancreatic islets and regulates β-cell function, apoptosis, and disease progression in children with new-onset T1D. In the present study, the objective was to investigate the expression patterns of all 15 known cathepsins in β-cell model systems and examine their role in the regulation of cytokine-induced apoptosis. Real-time qPCR screening of the cathepsins in human islets, 1.1B4 and INS-1E β-cell models identified several cathepsins that were expressed and regulated by pro-inflammatory cytokines. Using small interfering RNAs to knock down (KD) the cytokine-regulated cathepsins, we identified an anti-apoptotic function of cathepsin C as KD increased cytokine-induced apoptosis. KD of cathepsin C correlated with increased phosphorylation of JNK and p38 mitogen-activated protein kinases, and elevated chemokine CXCL10/IP-10 expression. This study suggests that cathepsin C is a modulator of β-cell survival, and that immune modulation of cathepsin expression in islets may contribute to immune-mediated β-cell destruction in T1D.

Indexed as

ApoptosisInsulin-Secreting CellsAnimalsCathepsin CCells, CulturedCytokinesDiabetes Mellitus, Type 1HumansIslets of LangerhansModels, BiologicalRatsCathepsin CCytokinesCTSCCXCL10human pancreatic isletsinflammationlysosomal proteasesMAPKpro-inflammatory cytokinestype 1 diabetesβ-cell death

Identifiers

PMID34828301
PMCPMC8622156
OpenAlexW3208896201

What OpenQuestion holds

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LicenceCC BY
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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.