Evidence map›Paper›PMID 42487268›Full record

ArticleEndocrinology, diabetes & metabolism2026

FZD7 Inhibitor SRI Attenuates High Glucose-Induced Retinal Pigment Epithelial Cell Injury Accompanied by Ferroptosis-Associated Changes via Suppression of the Wnt/β-Catenin Pathway.

Jiaojiao Jiang, Liu Zheng, Liwu Tan, Zhixiang Ding

Abstract read
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Article in Endocrinology, diabetes & metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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.

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Jiaojiao JiangDepartment of Ophthalmology, the First Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin, China.ORCID https://orcid.org/0000-0002-7595-0794
Liu ZhengDepartment of Ophthalmology, the First Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin, China.
Liwu TanDepartment of Cardiovascular, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, China.
Zhixiang DingDepartment of Ophthalmology, the First Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin, China.ORCID https://orcid.org/0000-0001-8573-8730

Funding

Graduate Research Program of Guilin Medical University GYBK2025003National Natural Science Foundation of China 82160197
6 · The paper itself

Abstract

purposeThis study investigated the protective effects of the Frizzled-7 (FZD7) inhibitor SRI against high glucose-induced injury in human retinal pigment epithelial (ARPE-19) cells. It also explored the underlying mechanism, focusing on whether SRI attenuates ferroptosis and apoptosis by inhibiting the Wnt/β-catenin signalling pathway.

methodsARPE-19 cells were exposed to high glucose (25 mM) and treated with a non-cytotoxic concentration of SRI (2 μmol/L), as determined by a CCK-8 assay. Wnt/β-catenin signalling was evaluated by measuring β-catenin expression and phosphorylation. The expression of GPX4, DHODH, and FSP1, together with intracellular Fe²⁺, ROS, and MDA levels, was assessed to evaluate ferroptosis and oxidative stress. Apoptosis was analysed by examining Bax and Bcl-2 expression, whereas mitochondrial ultrastructure was evaluated using quantitative transmission electron microscopy.

resultsUnder hyperglycaemic conditions, SRI suppressed Wnt/β-catenin signalling by reducing β-catenin expression and promoting its phosphorylation. SRI activated a GPX4-independent ferroptosis defence pathway, evidenced by increased DHODH and FSP1 expression without affecting GPX4 levels. Furthermore, SRI reduced intracellular Fe²⁺, ROS and MDA accumulation, downregulated Bax, upregulated Bcl-2 and improved mitochondrial morphology with partial restoration of cristae integrity. Collectively, these findings demonstrate that SRI alleviates high glucose-induced oxidative stress, ferroptosis, apoptosis and mitochondrial damage.

conclusionsSRI protects ARPE-19 cells from high glucose-induced injury by reducing ferroptosis-associated oxidative stress, apoptosis and mitochondrial dysfunction. These protective effects are mediated, at least in part, through inhibition of Wnt/β-catenin signalling and activation of a DHODH/FSP1-dependent but GPX4-independent ferroptosis defence pathway. These findings suggest that FZD7 represents a promising therapeutic target for diabetic retinopathy.

Indexed as

Diabetic RetinopathyEpithelial CellsFerroptosisFrizzled ReceptorsGlucoseRetinal Pigment EpitheliumWnt Signaling PathwayApoptosisbeta CateninCell LineHumansOxidative Stressbeta CateninFrizzled ReceptorsFZD7 protein, humanGlucosediabetic retinopathyferroptosisFZD7retinal pigment epithelial cellsWnt/β‐catenin pathway

Identifiers

PMID42487268
PMCPMC13392192

What Socratic holds

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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.