title: Tympanic membrane wound healing in rats assessed by transcriptome profiling.
abstract: OBJECTIVE
  The aim of this study is to elucidate transcriptional changes that occur in response to tympanic membrane (TM) perforation in rats and to infer key genes and molecular events in the healing process.
  
  
  METHODS
  A prospective cohort study of 393 male Sprague-Dawley (Rattus norvegicus) rats.
  
  
  METHODS
  Sprague-Dawley rats were randomly allocated into either control or perforation groups spanning a 7-day time period. Perforation groups consisted of 12-hour, 24-hour, 36-hour, 2-day, 3-day, 4-day, 5-day, six-day, and 7-day time points. The left TMs of all perforation groups were perforated and the RNA extracted at the specified time point postperforation. Subsequent analysis was performed using Agilent's 4 × 44 k whole rat genome arrays (40 in total) to assess wound-healing gene expression over a 7-day time period.
  
  
  RESULTS
  Over a 7-day time course and at nine time points that encompassed the wounding and progression of healing, a total of 3,262 genes were differentially expressed. In this study the transcripts most upregulated occurred at 12 hours. These were Stefin A2 (344-fold), Stefin 2 (143-fold), and Natriuretic peptide precursor type B (222-fold). Those most downregulated also occurred at 12 hours. These were alcohol dehydrogenase 7 (13.1-fold) and gamma-butyrobetaine hydroxylase (10.4-fold). Results were validated by quantitative real-time polymerase chain reaction.
  
  
  CONCLUSIONS
  The findings of this study provide a baseline against which to identify disease-related molecular signatures, biomarkers, and to develop new treatments for TM conditions based on molecular evidence.
authors.affiliation: Ear Sciences Centre, School of Surgery, The University of Western Australia, Perth, Australia. petersantamaria@hotmail.com
authors.forename: Peter L
authors.initials: PL
authors.lastname: Santa Maria
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Redmond
authors.forename: Russell L
authors.initials: RL
authors.lastname: McInnes
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Atlas
authors.forename: Reza
authors.initials: R
authors.lastname: Ghassemifar
mesh_terms: D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D016001:Confidence Intervals; D055312:Cystatin A / Q000235:genetics / Q000378:metabolism; D051187:Desmocollins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D046228:Microarray Analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D018058:Tympanic Membrane Perforation / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D014945:Wound Healing / Q000235:genetics* / Q000502:physiology
chemical_list: D055312:Cystatin A; D051187:Desmocollins; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D019278:Matrix Metalloproteinase 3