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Cited by 34Apelin-related biomedical researchRetinal Diseases and TreatmentsBarrier Structure and Function Studies

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Apelin-13 Is an Early Promoter of Cytoskeleton and Tight Junction in Diabetic Macular Edema via PI-3K/Akt and MAPK/Erk Signaling Pathways

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Li, Yang, Bai, Yu-jing, Jiang, Yan-rong, Yu, Wen-zhen, Shi, Xuan, Chen, Li, Feng, Jing, Sun, Gui-bo·2018·BioMed Research International
DOI 10.1155/2018/3242574PMC PMC5904819
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Abstract

Diabetic macular edema is major cause of vision loss associated with diabetic retinopathy. Breakdown of blood-retinal barrier, especially inner BRB, is an early event in pathogenesis of DR. Apelin, an endogenous ligand of APJ, mediates angiogenesis and is involved in the development of DR. The present study aimed to investigate effects and mechanism of apelin-13 in vascular permeability during DME. We verified apelin-13 was upregulated in DME patients’ vitreous. High glucose incubation led to a progressive increase of apelin-13, APJ, cytoskeleton, and tight junction proteins, including VE-Cadherin, FAK, Src, ZO-1, and occludin. Apelin-13 promoted HRMEC proliferation and migration and phosphorylation of both cytoskeleton and tight junction under both normal and high glucose conditions. Besides, apelin-13 activated PI-3K/Akt and MAPK/Erk signaling pathways, including PLC γ 1, p38, Akt, and Erk both in HRMEC and in C57BL/6 mice. Meanwhile, F13A performed opposite effects compared with apelin-13. In in vivo study, apelin-13 was also upregulated in retina of db/db mice. Taken together, apelin-13 increased biologic activity of HRMEC, as well as expression of both cytoskeleton and tight junction in DME via PI-3K/Akt and MAPK/Erk signaling pathways. Apelin-13 as an early promoter of vascular permeability may offer a new perspective strategy in early treatment of DR.

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  • A balanced p38/TXNIP/NFκB pathway inhibition is required for the prevention of macular edema.

    “and for the prevention of macular edema [ 88 , 89 , 90 , 91 ]”

    From MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges (2023) · cites this paper as [89]

    Results §3.7 (page unavailable) reports that inhibiting the apelin receptor reduced pathological retinal vascular permeability in diabetic mice and decreased phosphorylation of pathways including p38. This supports a possible approach to reducing edema-related leakage, but the paper does not establish that balanced p38/TXNIP/NFκB inhibition is required to prevent macular edema; TXNIP and that combined pathway are not reported. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Metadata

Authors
Li, Y., Bai, Y.-J., Jiang, Y.-R., Yu, W.-Z., Shi, X., Chen, L., Feng, J., & Sun, G.-B.
Affiliations
  • Peking University People's Hospital (CN)
  • Department of Ophthalmology, Peking University People’s Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing 100044, China
  • Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China
ORCID
Venue
BioMed Research International
Publisher
Wiley
Published
2018
Volume
2018
Pages
1-17
ISSN
  • 1110-7243 (ISSN-L)
  • 2314-6133
  • 2314-6141
DOI
10.1155/2018/3242574
PMC
PMC5904819
OpenAlex
W2796016821
Cited by
34
References
47
Citations by year
2025: 6 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 7 · 2020: 8 · 2019: 2 · 2018: 2
FWCI
3.07
Type
journal article
Language
en
Status
Retracted
Update notices
retraction (2026-03-31)
Open access
Licence
Locations
  • BioMed Research International (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (81271027, 2127000043)
  • EFSD/CDS/Lilly (81271027, 2127000043)
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Apelin-related biomedical research
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
apelin-13, diabetic macular edema, diabetic retinopathy, blood-retinal barrier, vascular permeability, cytoskeleton, tight junctions, PI3K/Akt signaling, ERK signaling, high glucose, VE-cadherin, occludin, ZO-1, focal adhesion kinase, Src kinase, PLCγ1, p38 MAPK, db/db mice, APJ receptor
MeSH terms
Apelin, Apelin Receptors, Adult, Aged, Animals, Capillary Permeability, Cell Movement, Cytoskeleton, Diabetic Retinopathy, Epithelial Cells, Female, Glucose, Humans, Macular Edema, Male, Mice, Inbred C57BL, Middle Aged, Phosphorylation, Vitreous Body, Tight Junctions, Phosphatidylinositol 3-Kinases, MAP Kinase Signaling System, Intercellular Signaling Peptides and Proteins, Cell Proliferation, Proto-Oncogene Proteins c-akt

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