ArticleMedical science monitor : international medical journal of experimental and clinical research2019
Angiopoietin-Like Protein 4 (ANGPTL4) Induces Retinal Pigment Epithelial Barrier Breakdown by Activating Signal Transducer and Activator of Transcription 3 (STAT3): Evidence from ARPE-19 Cells Under Hypoxic Condition and Diabetic Rats.
Article in Medical science monitor : international medical journal of experimental and clinical research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 21 citations in OpenAlex.
- PM2.5 exposure induces transcriptomic changes in ARPE-19 cells with activation of TGFβ-mediated signaling pathways: A next-generation sequencing approach.Journal of the Chinese Medical Association : JCMA · 2025Article
- Article
- Molecular Findings Before Vision Loss in the Streptozotocin-Induced Rat Model of Diabetic Retinopathy.Current issues in molecular biology · 2025Review
- Pemafibrate Induces a Low Level of PPARα Agonist-Stimulated mRNA Expression of ANGPTL4 in ARPE19 Cell.Bioengineering (Basel, Switzerland) · 2024Article
- The Role of Immune Cells and Signaling Pathways in Diabetic Eye Disease: A Comprehensive Review.Biomedicines · 2024Review
- The ANGPTL4-HIF-1α loop: a critical regulator of renal interstitial fibrosis.Journal of translational medicine · 2024Article
- Diabetes and high-glucose could upregulate the expression of receptor for activated C kinase 1 in retina.World journal of diabetes · 2024Article
- Angiopoietin-like protein 4 dysregulation in kidney diseases: a promising biomarker and therapeutic target.Frontiers in pharmacology · 2024Review
- Regulation of Long Noncoding RNA NEAT1/miR-320a/HIF-1α Competitive Endogenous RNA Regulatory Network in Diabetic Retinopathy.Investigative ophthalmology & visual science · 2023Article
- Article
- A Narrative Review of STAT Proteins in Diabetic Retinopathy: From Mechanisms to Therapeutic Prospects.Ophthalmology and therapy · 2022Review
- Clinical Comparative Study of Intravitreal Injection of Triamcinolone Acetonide and Aflibercept in the Treatment of Diabetic Retinopathy Cystoid Macular Edema.Emergency medicine international · 2022Article
- Aqueous Level of ANGPTL4 Correlates with the OCTA Metrics of Diabetic Macular Edema in NPDR.Journal of diabetes research · 2022Article
- Mangiferin inhibits cell migration and angiogenesis via PI3K/AKT/mTOR signaling in high glucose‑ and hypoxia‑induced RRCECs.Molecular medicine reports · 2021Article
- Aqueous angiopoietin-like levels correlate with optical coherence tomography angiography metrics in diabetic macular edema.International journal of ophthalmology · 2021Article
- Phosphorylation of STAT3 and ERBB2 mediates hypoxia‑induced VEGF release in ARPE‑19 cells.Molecular medicine reports · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND Diabetic retinopathy is a primary contributor of visual impairment in adult diabetes mellitus patients. Diabetic retinopathy causes breakdown of blood retinal barrier (BRB), and leads to diabetic macular edema. Previous studies have demonstrated angiopoietin-like protein 4 (ANGPTL4) as an effective diabetic retinopathy therapeutic target, however, its role in maintaining the outer BRB in diabetic retinopathy has yet not elucidated. MATERIAL AND METHODS We established an in vivo diabetic rat model with the use of streptozotocin injections and cultured ARPE-19 cells under (hypoxia, 1%) condition. We first investigated the expression of hypoxia induced factor-1alpha (HIF-1alpha) and ANGPTL4 in vivo and subsequently studied the transcriptional regulation and underlying molecular mechanisms in ARPE-19 cells under oxygen-deprived situations. RESULTS The expression of HIF-1alpha and ANGPTL4 was increased with diabetic retinopathy progression both in vivo and in vitro. Depletion of HIF-1alpha by siRNA inhibited hypoxia-induced ANGPTL4 expression. Repressing the HIF-1alpha/ANGPTL4 signaling effectively alleviated the migration and cellular permeability induced by hypoxia in ARPE-19 cells. Depletion of ANGPTL4 by siRNA significantly alleviated signal transducer and activator of transcription 3 (STAT3) activity in vitro, thereby attenuating the decrease of tight junction proteins occludin and zona occludens-1 (ZO-1) under hypoxia in ARPE-19 cells. CONCLUSIONS Our results suggest that ANGPTL4 partially modulates STAT3 and could serve as an effective diabetic retinopathy treatment strategy.
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