title: Effects of overexpressing FoxO1 on apoptosis in glomeruli of diabetic mice and in podocytes cultured in high glucose medium.
abstract: Podocyte apoptosis induced by high levels of glucose is a key event in the development and prognosis of diabetic nephropathy (DN). Forkhead transcription factor O1 (FoxO1) has been defined as a critical mediator of oxidative stress in animal models of diabetes and is involved in mitophagy. To test the role of FoxO1 in regulating podocyte apoptosis both in vivo and in vitro, we generated FoxO1 overexpression models. High-glucose (HG) induced podocyte apoptosis with decreased mitophagy. These changes were accompanied by mitochondrial dysfunction and more severe podocyte loss in mouse kidney. FoxO1 overexpression prevented the apoptosis induced by HG. Reduction of cell apoptosis and renal damage depended upon the expression of PTEN-induced putative kinase 1 (PINK1). These findings suggest that specific overexpression of renal FoxO1 decreases podocyte apoptosis, which may be explained in part by its regulation of PINK1, and that targeting FoxO1 may represent a novel therapeutic approach for DN.
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, 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, Henan Province, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Du
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, 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, Henan Province, 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, Henan Province, 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, Henan Province, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China.
authors.forename: Shuiying
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China.
authors.forename: Fengjuan
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China. Electronic address: hyqingj@zzu.edu.cn.
authors.forename: Guijun
authors.initials: G
authors.lastname: Qin
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000071161:Forkhead Box Protein O1 / Q000235:genetics* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D050199:Podocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D015854:Up-Regulation; D000099202:PTEN-Induced Putative Kinase
chemical_list: D000071161:Forkhead Box Protein O1; D005947:Glucose; D011494:Protein Kinases; D012333:RNA, Messenger; D000099202:PTEN-Induced Putative Kinase; C467200:Foxo1 protein, mouse
keywords: Apoptosis; Diabetic nephropathy; Forkhead-box class O1; Mitophagy; Podoctye