Evidence map›Paper›PMID 40753109›Full record

ArticleScientific reports2025

AMF30a promotes survival and function of human corneal endothelial cells by regulating TGF-β/ROCK/HIPPO pathway.

Yunkyoung Ryu, Hye-Jin Son, Jin Sun Hwang, Kyung Bo Noh, Sun-Hee Oh, Eun-Kyoung Choi, Young Joo Shin

Abstract read
In one paragraph

Article in Scientific reports, 2025. 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

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

1 citing paper in PubMed.

  1. Review
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

7 authors.

Yunkyoung Ryu *Department of Ophthalmology, Hallym University Medical Center, Hallym University College of Medicine, 1 Shingil-ro, Youngdeungpo-gu, Seoul, 07441, Republic of Korea.
Hye-Jin Son *Department of Ophthalmology, Hallym University Medical Center, Hallym University College of Medicine, 1 Shingil-ro, Youngdeungpo-gu, Seoul, 07441, Republic of Korea.
Jin Sun HwangDepartment of Ophthalmology, Hallym University Medical Center, Hallym University College of Medicine, 1 Shingil-ro, Youngdeungpo-gu, Seoul, 07441, Republic of Korea.
Kyung Bo NohHallym BioEyeTech Research Center, Hallym University College of Medicine, Seoul, Republic of Korea.
Sun-Hee OhDepartment of Ophthalmology, Hallym University Medical Center, Hallym University College of Medicine, 1 Shingil-ro, Youngdeungpo-gu, Seoul, 07441, Republic of Korea.
Eun-Kyoung ChoiIlsong Institute of Life Science, Hallym University, Seoul, Republic of Korea.
Young Joo ShinDepartment of Ophthalmology, Hallym University Medical Center, Hallym University College of Medicine, 1 Shingil-ro, Youngdeungpo-gu, Seoul, 07441, Republic of Korea. schinn@hanmail.net.

Funding

Hallym University Hallym University Research FundNational Research Foundation of Korea NRF-2023R1A2C2002674
6 · The paper itself

Abstract

Corneal endothelial cells (CECs), located in the innermost layer of cornea, are crucial for maintaining its transparency. Peptidylarginine deiminase 2 (PAD2) is an enzyme responsible for catalyzing the post-translational modification of arginine into citrulline, a process known as citrullination. In this study, we investigated the effect of AMF30a, PAD2 inhibitor, on survival and function of CECs. Cultured human CECs (hCECs) were treated with AMF30a, followed by treatments with or without AMF30a under transforming growth factor-beta (TGF-β). Cells were cultured from donor corneas and analyzed for viability (CCK-8), proliferation (BrdU assay), cytotoxicity (LDH assay), and oxidative stress (DCF-DA). Adhesion and morphology were evaluated via crystal violet staining and imaging software. Western blot and immunofluorescence identified protein expression and localization. RNA sequencing revealed differentially expressed genes, with functional enrichment via GO analysis. AMF30a enhanced cell viability, proliferation, and adhesion while reducing cytotoxicity and oxidative stress. Morphological analysis revealed reduced cell size and elongation factor, indicating structural changes. AMF30a modulated the HIPPO signaling pathway by increasing YAP phosphorylation and reducing its nuclear translocation, while downregulating ERK1/2 activation. Transcriptome analysis identified differentially expressed genes (DEGs) associated with AMF30a treatment, highlighting pathways related to GPCR signaling and protein targeting. Additionally, AMF30a counteracted TGF-β-induced effects, including increased oxidative stress, citrullination, and ROCK/HIPPO signaling activation, thereby promoting cell cycle progression and reducing senescence. PAD2-mediated citrullination is essential for TGF-β/ROCK/HIPPO signaling pathway. AMF30a promoted the proliferation and protected against TGF-β-induced senescence in hCECs, suggesting that PAD2 plays a significant role in the survival and function of hCECs. Thus, AMF30a may be a promising therapeutic strategy for hCEC diseases.

Indexed as

Endothelial CellsEndothelium, CornealProtein Serine-Threonine Kinasesrho-Associated KinasesSignal TransductionTransforming Growth Factor betaCell AdhesionCell ProliferationCells, CulturedCell SurvivalHippo Signaling PathwayHumansOxidative StressProtein-Arginine Deiminase Type 2Protein-Arginine Deiminase Type 2Protein Serine-Threonine Kinasesrho-Associated KinasesTransforming Growth Factor betaAMF30aCell deathHuman corneal endothelial cellsPAD2ProliferationTransforming growth factor-beta

Identifiers

PMID40753109
PMCPMC12317985

What Socratic 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 Socratic graph.