title: Conjunctival MicroRNA expression in inflammatory trachomatous scarring.
abstract: OBJECTIVE
  Trachoma is a fibrotic disease of the conjunctiva initiated by Chlamydia trachomatis infection. This blinding disease affects over 40 million people worldwide yet the mechanisms underlying its pathogenesis remain poorly understood. We have investigated host microRNA (miR) expression in health (N) and disease (conjunctival scarring with (TSI) and without (TS) inflammation) to determine if these epigenetic differences are associated with pathology.
  
  
  METHODS
  We collected two independent samples of human conjunctival swab specimens from individuals living in The Gambia (n = 63 & 194). miR was extracted, and we investigated the expression of 754 miR in the first sample of 63 specimens (23 N, 17 TS, 23 TSI) using Taqman qPCR array human miRNA genecards. Network and pathway analysis was performed on this dataset. Seven miR that were significantly differentially expressed between different phenotypic groups were then selected for validation by qPCR in the second sample of 194 specimens (93 N, 74 TS, 22 TSI).
  
  
  RESULTS
  Array screening revealed differential expression of 82 miR between N, TS and TSI phenotypes (fold change >3, p<0.05). Predicted mRNA targets of these miR were enriched in pathways involved in fibrosis and epithelial cell differentiation. Two miR were confirmed as being differentially expressed upon validation by qPCR. miR-147b is significantly up-regulated in TSI versus N (fold change = 2.3, p = 0.03) and miR-1285 is up-regulated in TSI versus TS (fold change = 4.6, p = 0.005), which was consistent with the results of the qPCR array.
  
  
  CONCLUSIONS
  miR-147b and miR-1285 are up-regulated in inflammatory trachomatous scarring. Further investigation of the function of these miR will aid our understanding of the pathogenesis of trachoma.
authors.affiliation: Department of Clinical Research, Faculty of Infectious Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Tamsyn
authors.initials: T
authors.lastname: Derrick
authors.forename: Chrissy h
authors.initials: Ch
authors.lastname: Roberts
authors.forename: Megha
authors.initials: M
authors.lastname: Rajasekhar
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Burr
authors.forename: Hassan
authors.initials: H
authors.lastname: Joof
authors.forename: Pateh
authors.initials: P
authors.lastname: Makalo
authors.forename: Robin L
authors.initials: RL
authors.lastname: Bailey
authors.forename: David C W
authors.initials: DC
authors.lastname: Mabey
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Burton
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Holland
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002692:Chlamydia trachomatis / Q000472:pathogenicity; D002921:Cicatrix / Q000473:pathology*; D003228:Conjunctiva / Q000473:pathology*; D005260:Female; D005714:Gambia; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D046228:Microarray Analysis; D008875:Middle Aged; D057089:Pathology, Molecular; D060888:Real-Time Polymerase Chain Reaction; D014141:Trachoma / Q000473:pathology*; D055815:Young Adult
chemical_list: D035683:MicroRNAs