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

BioMed Research International
Yang LiGui-Bo Sun

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 PLCγ1, 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 signali...Continue Reading

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Citations

Dec 27, 2018·Journal of Cellular Physiology·Jun ChengLinxi Chen
Jul 31, 2020·Investigative Ophthalmology & Visual Science·Jing FengYong Tao
Mar 27, 2020·Frontiers in Immunology·Kristian-Christos NgamsriFranziska M Konrad

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Methods Mentioned

BETA
Assay
fluorescence microscopy
PCR
protein assay
biopsy

Software Mentioned

NIS
GraphPad
Elements Imaging Software
Prism
SPSS17

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