title: TSC-22 up-regulates collagen 3a1 gene expression in the rat heart.
abstract: BACKGROUND
  The transforming growth factor (TGF)-β is one of the key mediators in cardiac remodelling occurring after myocardial infarction (MI) and in hypertensive heart disease. The TGF-β-stimulated clone 22 (TSC-22) is a leucine zipper protein expressed in many tissues and possessing various transcription-modulating activities. However, its function in the heart remains unknown.
  
  
  METHODS
  The aim of the present study was to characterize cardiac TSC-22 expression in vivo in cardiac remodelling and in myocytes in vitro. In addition, we used TSC-22 gene transfer in order to examine the effects of TSC-22 on cardiac gene expression and function.
  
  
  RESULTS
  We found that TSC-22 is rapidly up-regulated by multiple hypertrophic stimuli, and in post-MI remodelling both TSC-22 mRNA and protein levels were up-regulated (4.1-fold, P <0.001 and 3.0-fold, P <0.05, respectively) already on day 1. We observed that both losartan and metoprolol treatments reduced left ventricular TSC-22 gene expression. Finally, TSC-22 overexpression by local intramyocardial adenovirus-mediated gene delivery showed that TSC-22 appears to have a role in regulating collagen type IIIα1 gene expression in the heart.
  
  
  CONCLUSIONS
  These results demonstrate that TSC-22 expression is induced in response to cardiac overload. Moreover, our data suggests that, by regulating collagen expression in the heart in vivo, TSC-22 could be a potential target for fibrosis-preventing therapies.
authors.affiliation: Research Unit of Biomedicine (Pharmacology & Toxicology), University of Oulu, Oulu, Finland.
authors.forename: Annina
authors.initials: A
authors.lastname: Kelloniemi
authors.affiliation: Research Unit of Biomedicine (Pharmacology & Toxicology), University of Oulu, Oulu, Finland.
authors.forename: Jani
authors.initials: J
authors.lastname: Aro
authors.affiliation: Department of Pathology, Institute of Diagnostics, Oulu University Hospital, University of Oulu, Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Näpänkangas
authors.affiliation: Research Unit of Biomedicine (Pharmacology & Toxicology), University of Oulu, Oulu, Finland.
authors.forename: Elina
authors.initials: E
authors.lastname: Koivisto
authors.affiliation: Research Unit of Biomedicine (Pharmacology & Toxicology), University of Oulu, Oulu, Finland.
authors.forename: Erja
authors.initials: E
authors.lastname: Mustonen
authors.affiliation: Research Unit of Biomedicine (Pharmacology & Toxicology), University of Oulu, Oulu, Finland.|Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Ruskoaho
authors.affiliation: Research Unit of Biomedicine (Pharmacology & Toxicology), University of Oulu, Oulu, Finland. jaana.rysa@uef.fi.|School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland. jaana.rysa@uef.fi.
authors.forename: Jaana
authors.initials: J
authors.lastname: Rysä
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002478:Cells, Cultured; D024061:Collagen Type III / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use; D032342:Muscle Cells / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation; D020257:Ventricular Remodeling
chemical_list: D000959:Antihypertensive Agents; D024061:Collagen Type III; D012333:RNA, Messenger; D012097:Repressor Proteins; C490982:Tsc22d1 protein, rat; D008790:Metoprolol; D019808:Losartan