title: The role of FoxO1 in interleukin-1β-induced autostimulation in retina endothelial cells and retinas of diabetic rats.
abstract: Diabetic retinopathy is a chronic, low-grade inflammatory disease. The present study aimed to investigate the effect of forkhead transcription factor O1 (FoxO1) expression on interleukin-1β (IL-1β)-induced autostimulation, both in vitro in human retina microvascular endothelial cells (HRMECs), and in vivo in retinas isolated from streptozotocin-induced diabetic rats. High-glucose (HG) and recombinant IL-1β treatment were both shown to increase the expression of FoxO1 and IL-1β in HRMECs in a dose-dependent manner. IL-1 receptor antagonist (IL-1RA) and mitogen-activated protein kinase (MAPK) inhibitors reduced IL-1β-induced expression of FoxO1 in HRMECs. Moreover, the increased expressions of FoxO1 and IL-1β in the retinas of diabetic rats were significantly decreased by intravitreal injection of lentiviral vector-mediated FoxO1 small-interfering RNA. Together, these results suggest that HG triggers IL-1β synthesis in HRMECs. The produced IL-1β induces increased FoxO1 expression, as well as interacts with the IL-1 receptor to activate MAPK signaling and thereby induces IL-1β autostimulation. The IL-1β-induced autostimulation can be inhibited by downregulation of FoxO1, accompanied by a reduction of inflammation. Together, these findings identify novel functions for FoxO1 and IL-1β in diabetic retinopathy.
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Qingzhu
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Electronic address: hyqingj@zzu.edu.cn.
authors.forename: Guijun
authors.initials: G
authors.lastname: Qin
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003930:Diabetic Retinopathy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000071161:Forkhead Box Protein O1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; C508585:IL1B protein, human; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D009419:Nerve Tissue Proteins; D017472:Receptors, Interleukin-1; C074639:Foxo1 protein, rat; D020928:Mitogen-Activated Protein Kinases
keywords: Autostimulation; Diabetic retinopathy; Forkhead transcription factor O1; Inflammation; Interleukin-1β