Liraglutide prevents cellular senescence in human retinal endothelial cells (HRECs) mediated by SIRT1: an implication in diabetes retinopathy

• Published in: Human cell : official journal of Human Cell Research Society 2024-05, Vol.37 (3), p.666-674
• Main Authors: Hou, Lihua, Du, Jianying, Dong, Yongxiao, Wang, Min, Wang, Libo, Zhao, Jifei
• Format: Article
• Language: English
• Subjects: Aging; Biomedical and Life Sciences; Cell Biology; Cellular Senescence; Diabetes; Diabetes mellitus; Diabetes Mellitus - metabolism; Diabetic Retinopathy - drug therapy; Endothelial cells; Endothelial Cells - metabolism; Glucagon; Glucagon-like peptide 1; Glucose; Glucose - adverse effects; Glucose - metabolism; Gynecology; Homeostasis; Humans; Hyperglycemia; Interleukin 6; Life Sciences; Liraglutide - metabolism; Liraglutide - pharmacology; Liraglutide - therapeutic use; Metabolic disorders; Microvasculature; Oncology; Peptides; Reproductive Medicine; Research Article; Retina; Retinopathy; Risk factors; Senescence; SIRT1 protein; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Stem Cells; Surgery; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1749-0774; 0914-7470; 1749-0774
• DOI: 10.1007/s13577-024-01038-1

Diabetes mellitus (DM) is a chronic metabolic disorder affecting millions of people worldwide, characterized by dysregulated glucose homeostasis and hyperglycemia. Diabetic retinopathy (DR) is one of the serious multisystemic complications. Aging is an important risk factor for DR. Endothelial sirtuin 1 (SIRT1) plays an important role in regulating the pathophysiology of glucose metabolism, cellular senescence, and aging. Liraglutide, an analog of Glucagon-like peptide 1 (GLP-1), has been widely used in the treatment of DM. However, the effects of Liraglutide on DR are less reported. Here, we investigated whether treatment with Liraglutide has beneficial effects on high glucose (HG)-induced injury in human retinal microvascular endothelial cells (HRECs). First, we found that exposure to HG reduced the expression of glucagon-like peptide 1 receptor 1 (GLP-1R). Additionally, Liraglutide ameliorated HG-induced increase in the expression of vascular endothelial growth factor-A (VEGF-A) and interleukin 6 (IL-6). Importantly, Liraglutide ameliorated cellular senescence and increased telomerase activity in HG-challenged HRECs. Liraglutide also reduced the levels of p53 and p21. Mechanistically, Liraglutide restored the expression of SIRT1 against HG. In contrast, the knockdown of SIRT1 abolished the protective effects of Liraglutide in cellular senescence of HRECs. Our findings suggest that Liraglutide might possess a benefit on DR mediated by SIRT1.