title: FTO modulates fibrogenic responses in obstructive nephropathy.
abstract: Genome-wide association studies have shown that variants in fat mass and obesity-associated (FTO) gene are robustly associated with body mass index and obesity. These FTO variants are also associated with end stage renal disease and all-cause mortality in chronic kidney diseases. However, the exact role of FTO in kidneys is currently unknown. Here we show that FTO expression is increased after ureteral obstruction and renal fibrosis. Deficiency of the FTO gene attenuates the fibrogenic responses induced by ureteral obstruction in the kidney. Renal tubular cells deficient of FTO produce less α-SMA after TGF-β stimulation. FTO is indispensable for the extracellular matrix synthesis after ureteral obstruction in kidneys. Indeed, global gene transcriptions amplitude is reduced in FTO deficient kidneys after ureteral obstruction. These data establish the importance of FTO in renal fibrosis, which may have potential therapeutic implications.
authors.affiliation: Department of Cardiology, Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Taiwan.
authors.forename: Chao-Yung
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
authors.forename: Shian-Sen
authors.initials: SS
authors.lastname: Shie
authors.affiliation: Department of Cardiology, Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Taiwan.
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Tsai
authors.affiliation: Department of Cardiology, Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Taiwan.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Taiwan.
authors.forename: Kuo-Chun
authors.initials: KC
authors.lastname: Hung
authors.affiliation: Department of Cardiology, Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Taiwan.
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Taiwan.
authors.forename: I-Chang
authors.initials: IC
authors.lastname: Hsieh
authors.affiliation: Department of Cardiology, Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Taiwan.
authors.forename: Ming-Shien
authors.initials: MS
authors.lastname: Wen
mesh_terms: D000199:Actins / Q000378:metabolism; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D016000:Cluster Analysis; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis; D015870:Gene Expression; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications*
chemical_list: D000199:Actins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C524916:FTO protein, mouse; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO