ArticleBMJ open diabetes research & care2020
Histamine causes an imbalance between pro-angiogenic and anti-angiogenic factors in the retinal pigment epithelium of diabetic retina via H4 receptor/p38 MAPK axis.
Article in BMJ open diabetes research & care, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Article
- Amine-responsive Rhodopsin-like GPCRs in ocular pathology: mechanistic associations, candidate biomarkers, and therapeutic potential.Frontiers in physiology · 2026Review
- Atypical p38 Kinase Signaling in Retinal Vascular Damage and Recovery.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Aqueous Humor Metabolomics in Different Stages of Diabetic Retinopathy Based on Ultra - Performance Liquid Chromatography - Tandem Mass Spectrometry.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Effect of different salt additions on the taste and flavor-related compounds in chicken soup.Frontiers in nutrition · 2024Article
- Increased postoperative glycemic variability is associated with increased mortality in diabetic patients undergoing hip arthroplasty for hip fracture.Archives of orthopaedic and trauma surgery · 2023Article
- Circ_001209 aggravates diabetic retinal vascular dysfunction through regulating miR-15b-5p/COL12A1.Journal of translational medicine · 2021Article
- Atypical p38 Signaling, Activation, and Implications for Disease.International journal of molecular sciences · 2021Review
- Primaquine Diphosphate, a Known Antimalarial Drug, Blocks Vascular Leakage Acting Through Junction Stabilization.Frontiers in pharmacology · 2021Article
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Authors and funding
10 authors at 5 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
introductionSystemic histaminergic activity is elevated in patients with diabetes mellitus. There are a few studies suggesting that histamine is implicated in the pathogenesis of diabetes, but the exact role of histamine in the development of diabetic retinopathy is unclear. The aim of this study was to investigate the role of histamine receptor H4 (HRH4) in the regulation of retinal pigment epithelium (RPE)-derived pro-angiogenic and anti-angiogenic factors under diabetic conditions. RESEARCH DESIGN AND
methodsThe levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), histamine and histidine decarboxylase (HDC) in the serum and vitreous samples of patients with diabetes were compared with those of patients without diabetes. The effect of hyperglycemia on expression levels of HRH4, VEGF, IL-6 and pigment epithelium-derived factor (PEDF) in the RPE was determined. The role of HRH4 in high glucose-induced regulation of VEGF, IL-6 and PEDF in ARPE-19 cells and the underlying regulatory mechanism were verified using an RNA interference-mediated knockdown study.
resultsThe serum and vitreous levels of VEGF, IL-6, histamine and HDC were more increased in patients with diabetic retinopathy than in patients without diabetes. HRH4 was overexpressed in RPE both in vitro and in vivo. Histamine treatment upregulated VEGF and IL-6 and downregulated PEDF expression in ARPE-19 cells cultivated under hyperglycemic conditions. Hyperglycemia-induced phosphorylation of p38 and subsequent upregulation of VEGF and IL-6 and downregulation of PEDF were dampened by small interfering RNA-mediated knockdown of HRH4 in ARPE-19 cells.
conclusionsTaken together, HRH4 was a critical regulator of VEGF, IL-6 and PEDF in the RPE under hyperglycemic conditions and the p38 mitogen-activated protein kinase pathway mediated this regulatory mechanism.
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