title: Fibroblast growth factor 21 deletion aggravates diabetes-induced pathogenic changes in the aorta in type 1 diabetic mice.
abstract: Fibroblast growth factor 21 (FGF21) is an important regulator in glucose and lipid metabolism, and has been considered as a potential therapy for diabetes. The effect of FGF21 on the development and progression of diabetes-induced pathogenic changes in the aorta has not currently been addressed. To characterize these effects, type 1 diabetes was induced in both FGF21 knockout (FGF21KO) and C57BL/6 J wild type (WT) mice via multiple-dose streptozotocin injection. FGF21KO diabetic mice showed both earlier and more severe aortic remodeling indicated by aortic thickening, collagen accumulation and fibrotic mediator connective tissue growth factor expression. This was accompanied by significant aortic cell apoptosis than in WT diabetic mice. Further investigation found that FGF21 deletion exacerbated aortic inflammation and oxidative stress reflected by elevated expression of tumor necrosis factor α and transforming growth factor β, and the accumulation of 3-nitrotyrocine and 4-Hydroxynonenal. FGF21 administration can reverse the pathologic changes in FGF21KO diabetic mice. These findings demonstrate that FGF21 deletion aggravates aortic remodeling and cell death probably via exacerbation of aortic inflammation and oxidative stress. This marks FGF21 as a potential therapy for the treatment of aortic damage due to diabetes.
authors.affiliation: Chinese-American Research Institute for Diabetic Complications at the Wenzhou Medical University, Wenzhou, China.|Chinese-American Research Institute for Pediatrics of the First Affiliated Hospital at the Wenzhou Medical University, Wenzhou, China.|Department of Endocrinology, the Third Hospital Affiliate to Wenzhou Medical University, Ruian, China.|Kosair Children's Hospital Research Institute, the Department of Pediatrics of the University of Louisville, School of Medicine, Louisville, USA.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Yan
authors.affiliation: Chinese-American Research Institute for Diabetic Complications at the Wenzhou Medical University, Wenzhou, China.|Kosair Children's Hospital Research Institute, the Department of Pediatrics of the University of Louisville, School of Medicine, Louisville, USA.|School of Nursing, Wenzhou Medical University, Wenzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Chinese-American Research Institute for Diabetic Complications at the Wenzhou Medical University, Wenzhou, China.|Department of Endocrinology, the Third Hospital Affiliate to Wenzhou Medical University, Ruian, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Kosair Children's Hospital Research Institute, the Department of Pediatrics of the University of Louisville, School of Medicine, Louisville, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Kosair Children's Hospital Research Institute, the Department of Pediatrics of the University of Louisville, School of Medicine, Louisville, USA.|Departments of Cardiovascular Disorders and Geriatrics of the First Hospital of Jilin University, Changchun, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Kosair Children's Hospital Research Institute, the Department of Pediatrics of the University of Louisville, School of Medicine, Louisville, USA.|Departments of Cardiovascular Disorders and Geriatrics of the First Hospital of Jilin University, Changchun, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, the Third Hospital Affiliate to Wenzhou Medical University, Ruian, China.
authors.forename: Xuemian
authors.initials: X
authors.lastname: Lu
authors.affiliation: Kosair Children's Hospital Research Institute, the Department of Pediatrics of the University of Louisville, School of Medicine, Louisville, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Toxicology of the University of Louisville School of Medicine, Louisville, USA.
authors.forename: Wenke
authors.initials: W
authors.lastname: Feng
authors.affiliation: Chinese-American Research Institute for Diabetic Complications at the Wenzhou Medical University, Wenzhou, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.affiliation: Chinese-American Research Institute for Diabetic Complications at the Wenzhou Medical University, Wenzhou, China. y0tan002@louisville.edu.|Chinese-American Research Institute for Pediatrics of the First Affiliated Hospital at the Wenzhou Medical University, Wenzhou, China. y0tan002@louisville.edu.|Kosair Children's Hospital Research Institute, the Department of Pediatrics of the University of Louisville, School of Medicine, Louisville, USA. y0tan002@louisville.edu.|Department of Pharmacology and Toxicology of the University of Louisville School of Medicine, Louisville, USA. y0tan002@louisville.edu.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D017209:Apoptosis; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D005346:Fibroblast Growth Factors / Q000008:administration & dosage / Q000172:deficiency* / Q000235:genetics; D005355:Fibrosis; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D010641:Phenotype; D015398:Signal Transduction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D066253:Vascular Remodeling
chemical_list: D000447:Aldehydes; C526318:CCN2 protein, mouse; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C414620:fibroblast growth factor 21; D055513:Connective Tissue Growth Factor; C002744:3-nitrotyrosine; D014443:Tyrosine; D005346:Fibroblast Growth Factors; D003094:Collagen; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; C027576:4-hydroxy-2-nonenal
keywords: Diabetes; Fibroblast growth factor 21; Oxidative stress; Vascular damage