title: "Hypoxia-induced down-regulation of microRNA-449a/b impairs control over targeted SERPINE1 (PAI-1) mRNA - a mechanism involved in SERPINE1 (PAI-1) overexpression".
abstract: BACKGROUND
  In damaged organs tissue repair and replacement of cells by connective tissue provokes a response of fibroblasts to cellular stress factors such as hypoxia.MicroRNAs (miRNA) are small non-coding RNA molecules which bind to their mRNA targets which eventually lead to repression of translation. Whether the response of fibroblasts to stress factors also involves the miRNA system is largely unknown.
  
  
  RESULTS
  By miRNA profiling we identified down-regulation of miRNA-449a/b expression in hypoxic fibroblasts. Specific miRNA inhibitors and mimics showed direct evidence for targeting the serine protease inhibitor (serpin) protein (SERPINE1; plasminogen activator inhibitor-1, PAI-1) by miRNA-449a/b leading to SERPINE1 mRNA and protein up- and down-regulation, respectively. SERPINE1 expression in vivo could be located predominantly in areas of fibrosis and remodeling.
  
  
  CONCLUSIONS
  Our study offers serious lines of evidence for a novel hypoxia-dependent mechanism involving hypoxia-induced decrease of clustered miRNA-449a/b, hypoxia-induced amplification of concomitant increase of targeted SERPINE1 (PAI-1) and its overexpression in tissues showing a hypoxic environment.
authors.affiliation: Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Muth
authors.forename: Katharina
authors.initials: K
authors.lastname: Theophile
authors.forename: Kais
authors.initials: K
authors.lastname: Hussein
authors.forename: Christoph
authors.initials: C
authors.lastname: Jacobi
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
authors.forename: Oliver
authors.initials: O
authors.lastname: Bock
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D016030:Kidney Transplantation; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D014184:Transplantation, Homologous / Q000473:pathology
chemical_list: C544530:MIRN449 microRNA, human; D035683:MicroRNAs; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger