Evidence map›Paper›PMID 27878968›Full record

ArticleJournal of tissue engineering and regenerative medicine2017

Proprotein convertase inhibition promotes ciliated cell differentiation - a potential mechanism for the inhibition of Notch1 signalling by decanoyl-RVKR-chloromethylketone.

Sang-Nam Lee, In-Suk Choi, Hyun Jun Kim, Eun Jin Yang, Hyun Jin Min, Joo-Heon Yoon

Open access · hybridAbstract read
In one paragraph

Article in Journal of tissue engineering and regenerative medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.3field-weighted citation impact, top 30% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Furin as a therapeutic target in cystic fibrosis airways disease.European respiratory review : an official journal of the European Respiratory Society · 2023
    Review
  3. Review
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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

6 authors at 4 institutions in 1 country.

Sang-Nam LeeResearch Centre for Human Natural Defence System, Yonsei University College of Medicine, Seoul, Korea.
In-Suk ChoiResearch Centre for Human Natural Defence System, Yonsei University College of Medicine, Seoul, Korea.
Hyun Jun KimDepartment of Otorhinolaryngology, School of Medicine, Ajou University, Seoul, Korea.
Eun Jin YangClinical Research Division, Korea Institute of Oriental Medicine, Seoul, Korea.
Hyun Jin MinDepartment of Otorhinolaryngology-Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Korea.
Joo-Heon YoonResearch Centre for Human Natural Defence System, Yonsei University College of Medicine, Seoul, Korea.
Yonsei University · KRChung-Ang University · KRKorea Institute of Oriental Medicine · KRSejong University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic repetitive rounds of injury and repair in the airway lead to airway remodelling, including ciliated cell loss and mucous cell hyperplasia. Airway remodelling is mediated by many growth and differentiation factors including Notch1, which are proteolytically processed by proprotein convertases (PCs). The present study evaluated a novel approach for controlling basal cell-type determination based on the inhibition of PCs. It was found that decanoyl-RVKR-chloromethylketone (CMK), a PC inhibitor, promotes ciliated cell differentiation and has no effect on the ciliary beat frequency in air-liquid interface (ALI) cultures of human nasal epithelial cells (HNECs). Comparative microarray analysis revealed that CMK considerably increases ciliogenesis-related gene expression. Use of cell-permeable and cell-impermeable PC inhibitors suggests that intracellular PCs regulate basal cell-type determination in ALI culture. Furthermore, CMK effect on ciliated cell differentiation was reversed by a Notch inhibitor N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT). CMK inhibited the processing of Notch1, a key regulator of basal cell differentiation toward secretory cell lineages in the airway epithelium, and down-regulated the expression of Notch1 target genes together with furin, a PC. Specific lentiviral shRNA-mediated knockdown of furin resulted in reduced Notch1 processing and increased numbers of ciliated cells in HNECs. Moreover, CMK inhibited Notch1 processing and promoted regeneration and ciliogenesis of the mouse nasal respiratory epithelium after ZnSO

Indexed as

Amino Acid Chloromethyl KetonesCell DifferentiationCiliaEpithelial CellsFurinHumansNasal MucosaProprotein ConvertasesProtein Synthesis InhibitorsReceptor, Notch1Amino Acid Chloromethyl KetonesFurinFURIN protein, humanNOTCH1 protein, humanProprotein ConvertasesProtein Synthesis InhibitorsReceptor, Notch1airway remodellingbasal progenitor cellsciliated cell differentiationcultured human nasal epithelial cellsnotch1proprotein convertases

Identifiers

PMID27878968
PMCPMC6214225
OpenAlexW2549829371

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.