Evidence map›Paper›PMID 37190063›Full record

ArticleCells2023

IKKβ Inhibition Attenuates Epithelial Mesenchymal Transition of Human Stem Cell-Derived Retinal Pigment Epithelium.

Srinivasa R Sripathi, Ming-Wen Hu, Ravi Chakra Turaga, Rebekah Mikeasky, Ganesh Satyanarayana, Jie Cheng, Yukan Duan, Julien Maruotti, Karl J Wahlin, Cynthia A Berlinicke and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

8 citing papers in PubMed, 16 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

13 authors at 4 institutions in 1 country.

Srinivasa R SripathiDepartment of Ophthalmology, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.ORCID 0000-0001-6834-553X
Ming-Wen HuDepartment of Ophthalmology, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Ravi Chakra TuragaCaris Life Sciences, 350 W Washington St., Tempe, AZ 85281, USA.ORCID 0000-0001-9075-7645
Rebekah MikeaskyDepartment of Ophthalmology, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Ganesh SatyanarayanaDepartment of Biology, Georgia State University, Atlanta, GA 30303, USA.ORCID 0000-0002-1136-1990
Jie ChengDepartment of Ophthalmology, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Yukan DuanDepartment of Ophthalmology, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Julien MaruottiResearch and Development, Phenocell, 06130 Grasse, France.
Karl J WahlinShiley Eye Institute, University of California, San Diego, CA 92093, USA.ORCID 0000-0002-0494-8304
Cynthia A BerlinickeDepartment of Ophthalmology, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jiang QianDepartment of Ophthalmology, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Noriko EsumiDepartment of Ophthalmology, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.ORCID 0000-0001-7995-4023
Donald J ZackDepartment of Ophthalmology, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Johns Hopkins University · USEmory University · USGeorgia State University · USUniversity of California San Diego · US

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Ji Yi · 1985 to 2026
$22.1M
Role of OPA1 in Retinal Ganglion Cell Differentiation and the Pathogenesis of Dominant Optic AtrophyR01EY031714 · NEI · JOHNS HOPKINS UNIVERSITY · PI Donald J. Zack · 2022 to 2026
$2.0M
NEI NIH HHS P30 EY001765NEI NIH HHS R01 EY031714
6 · The paper itself

Abstract

Epithelial-mesenchymal transition (EMT), which is well known for its role in embryonic development, malignant transformation, and tumor progression, has also been implicated in a variety of retinal diseases, including proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD), and diabetic retinopathy. EMT of the retinal pigment epithelium (RPE), although important in the pathogenesis of these retinal conditions, is not well understood at the molecular level. We and others have shown that a variety of molecules, including the co-treatment of human stem cell-derived RPE monolayer cultures with transforming growth factor beta (TGF-β) and the inflammatory cytokine tumor necrosis factor alpha (TNF-α), can induce RPE-EMT; however, small molecule inhibitors of RPE-EMT have been less well studied. Here, we demonstrate that BAY651942, a small molecule inhibitor of nuclear factor kapa-B kinase subunit beta (IKKβ) that selectively targets NF-κB signaling, can modulate TGF-β/TNF-α-induced RPE-EMT. Next, we performed RNA-seq studies on BAY651942 treated hRPE monolayers to dissect altered biological pathways and signaling events. Further, we validated the effect of IKKβ inhibition on RPE-EMT-associated factors using a second IKKβ inhibitor, BMS345541, with RPE monolayers derived from an independent stem cell line. Our data highlights the fact that pharmacological inhibition of RPE-EMT restores RPE identity and may provide a promising approach for treating retinal diseases that involve RPE dedifferentiation and EMT.

Indexed as

Retinal Pigment EpitheliumVitreoretinopathy, ProliferativeEpithelial-Mesenchymal TransitionHumansI-kappa B KinaseProtein Serine-Threonine KinasesStem CellsTransforming Growth Factor betaTumor Necrosis Factor-alphaI-kappa B KinaseProtein Serine-Threonine KinasesTransforming Growth Factor betaTumor Necrosis Factor-alphadifferentiationepithelial-mesenchymal transitionkinase inhibitorsPVR and AMDretinal pigment epitheliumstem cellsTGF–β/–αtranscriptomics

Identifiers

PMID37190063
PMCPMC10136838
OpenAlexW4365515369

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.