Exendin-4 and GLP-1 decreases induced expression of ICAM-1, VCAM-1 and RAGE in human retinal pigment epithelial cells
Abstract
Background Advanced glycation end products (AGEs) take part in the development of diabetic retinopathy. Hyperglycemia triggers an inflammatory response in the retina. These mechanisms may lead to an enhanced expression of adhesion molecules (ICAM-1 and VCAM-1) in human retinal pigment epithelium (HRPE). Glucagon-like peptide 1 (GLP-1) functions as an incretin hormone with antidiabetogenic properties. GLP-1 also possesses vasoprotective properties. Methods The aim of our study was to evaluate the influence of glycated albumin (GlyAlb; 100; 500 and 1000 mg/l) and pro-inflammatory cytokine, TNF-α (2.5 and 10 ng/ml), on expression of RAGE, ICAM-1 and VCAM-1 and to evaluate the influence of GLP-1 (100 nM) and its analogue, exendin-4 (10 nM), on the expression of RAGE, ICAM-1 and VCAM-1 in stimulated HRPE. Results TNF-α increased RAGE expression in HRPE cells. The addition of GlyAlb (500 and 1000 mg/l) resulted in a decrease of RAGE expression. Both TNF-α and GlyAlb increased the secretion of both adhesion molecules. In cells co-treated with GLP-1 or exendin-4 both incretins decreased RAGE expression in TNF-α treated cells, and in GlyAlb group. The ICAM-1 expression was lowered by exendin-4 and GLP-1 in cells stimulated by TNF-α and GlyAlb. The similar results were obtained for VCAM-1. All observed alterations were statistically significant. Conclusions The obtained results indicate that both GLP-1 and exendin-4 by decreasing the expression of RAGE in HRPE can make these cells more resistant to circulating AGEs, and decreased expression of circulating VCAM-1 and ICAM-1, can be the result of anti-inflammatory properties of incretins and decreased expression of RAGE.
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GLP-1 therapy may be beneficial for the treatment of chronic inflammatory diseases including nonalcoholic steatohepatitis, atherosclerosis, neurodegenerative disorders, diabetic nephropathy, asthma, and psoriasis.
“Thus, GLP-1 therapy may be beneficial for the treatment of chronic inflammatory diseases including nonalcoholic steatohepatitis, atherosclerosis, neurodegenerative disorders, diabetic nephropathy, asthma, and psoriasis [14, 26–32].”
From Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control (2016) · cites this paper as [32]
GLP-1 (100 nM) or exendin-4 (10 nM) treatment inhibited TNF-α-induced expression of RAGE, ICAM-1, and VCAM-1 in human retinal pigment epithelial cells.
“GLP-1 (100 nM) or exendin-4 (10 nM) treatment inhibited TNF-α-induced expression of receptor for advanced glycation end products (RAGE), ICAM-1, and VCAM-1 in human retinal pigment epithelial cells [32]”
From Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control (2016) · cites this paper as [32]
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References 47 · Cited by 36
- Authors
- Dorecka, M., Siemianowicz, K., Francuz, T., Garczorz, W., Chyra, A., Klych, A., & Romaniuk, W.
- Affiliations
- Medical University of Silesia (PL)
- Corresponding author
- Siemianowicz, Krzysztof
- Venue
- Pharmacological Reports
- Published
- 2013-07
- Volume
- 65
- Issue
- 4
- Pages
- 884-890
- ISSN
- 1734-1140 (ISSN-L)
- OpenAlex
- W2000067040
- Cited by
- 36
- References
- 47
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 2
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacological Reports (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- exendin-4, glucagon-like peptide-1, retinal pigment epithelium, ICAM-1, VCAM-1, RAGE, advanced glycation end products, glycated albumin, TNF-α, diabetic retinopathy, incretins, adhesion molecules, inflammation
- MeSH terms
- Receptor for Advanced Glycation End Products, Exenatide, Glycated Serum Albumin, Cells, Cultured, Dose-Response Relationship, Drug, Humans, Peptides, Receptors, Immunologic, Serum Albumin, Tumor Necrosis Factor-alpha, Venoms, Glycation End Products, Advanced, Intercellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, Glucagon-Like Peptide 1, Retinal Pigment Epithelium
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