title: MicroRNA regulation of unfolded protein response transcription factor XBP1 in the progression of cardiac hypertrophy and heart failure in vivo.
abstract: BACKGROUND
  XBP1 is a key transcription factor of the unfolded protein response in mammalian cells, which is involved in several cardiovascular pathological progression including cardiac hypertrophy and myocardial infarction, but its expression trend, function and upstream regulate mechanism in the development of heart failure are unclear. In the present study, therefore, the potential role of miRNAs in the regulation of XBP1 expression in heart failure was examined.
  
  
  RESULTS
  First, western blots showed that cardiac expression of ER stress marker XBP1 were induced in the early adaptive phase, but decreased in the maladaptive phase in hypertrophic and failing heart, while there was no obvious change of upstream ATF6 and IRE1 activity in this progression. Interestingly, we further found that XBP1 and its downstream target VEGF were attenuated by miR-30* and miR-214 in cardiomyocyte. Moreover, we found that miR-30* was significantly reduced in the early phase of cardiac hypertrophic animal model and in human failing hearts, while both miR-214 and miR-30* were increased in the maladaptive diseased heart, thereby contribute to impairment of cardiac XBP1 and VEGF expression.
  
  
  CONCLUSIONS
  These results provide the first clear link between miRNAs and direct regulation of XBP1 in heart failure and reveal that miR-214 and miR-30* synergistically regulates cardiac VEGF expression and angiogenesis by targeting XBP1 in the progression from adaptive hypertrophy to heart failure.
authors.affiliation: Department of Internal Medicine and the Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, 430030, Wuhan, People's Republic of China. duanquanlu@163.com.
authors.forename: Quanlu
authors.initials: Q
authors.lastname: Duan
authors.affiliation: Department of Internal Medicine and the Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, 430030, Wuhan, People's Republic of China. chenchen@tjh.tjmu.edu.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine and the Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, 430030, Wuhan, People's Republic of China. wayl0808@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine and the Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, 430030, Wuhan, People's Republic of China. nili23@126.com.
authors.forename: Ni
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Internal Medicine and the Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, 430030, Wuhan, People's Republic of China. gongwei19860826@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: Department of Internal Medicine and the Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, 430030, Wuhan, People's Republic of China. shengli410@126.com.
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Internal Medicine and the Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, 430030, Wuhan, People's Republic of China. dwwang@tjh.tjmu.edu.cn.
authors.forename: Dao Wen
authors.initials: DW
authors.lastname: Wang
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology*; D018450:Disease Progression; D006333:Heart Failure / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007545:Isoproterenol / Q000008:administration & dosage; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000502:physiology*; D056811:Unfolded Protein Response; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D035683:MicroRNAs; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C000605545:Xbp1 protein, rat; D007545:Isoproterenol