title: Global expression of molecular transporters in the human vaginal tract: implications for HIV chemoprophylaxis.
abstract: BACKGROUND
  Pre-exposure chemoprophylaxis (PrECP) using antiretroviral agents is a promising strategy for the prevention of sexual HIV transmission in women. Molecular transporters in the human vaginal tract (VT) may play a pivotal role in determining drug disposition and, consequently, pharmacodynamic outcomes in these efforts. Little is known, however, on the expression of these transporters in vaginal tissues, representing a critical knowledge gap.
  
  
  RESULTS
  Our study analyzed the genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women undergoing gynecologic surgeries. The analysis revealed that, unexpectedly, a large number (43%) of gene isoforms corresponding to membrane transporters were over-expressed (above the median expression level) in all samples. A subset of 12 highly expressed membrane transporters was identified and contained 10 members (83%) of the solute carrier superfamily. The largest difference in membrane transporter gene expression was observed across subjects, but more subtle differential expression also was found along the anterior-posterior axis of the VT. Cross-validation of the microarray analyses with measurements RT-qPCR demonstrated high concordance between these data sets. Immunofluorescence labeling of membrane transporter proteins in vaginal tissues was highly dependent on tissue/cell types.
  
  
  CONCLUSIONS
  Antiretroviral PrECP drugs currently under evaluation are substrates for molecular transporters that were commonly expressed, but fell into both over- or under-expressed categories in all samples, suggesting a complex role for carrier-mediated processes in determining the disposition of these xenobiotics in vaginal tissues. These findings hold important implications for the successful development of products, either oral or intravaginal, for female-controlled HIV PrECP.
authors.affiliation: Department of Chemistry, Oak Crest Institute of Science, Pasadena, California, United States of America.
authors.forename: Manjula
authors.initials: M
authors.lastname: Gunawardana
authors.forename: Madeline
authors.initials: M
authors.lastname: Mullen
authors.forename: John A
authors.initials: JA
authors.lastname: Moss
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pyles
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Nusbaum
authors.forename: Jignesh
authors.initials: J
authors.lastname: Patel
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Vincent
authors.forename: Charles
authors.initials: C
authors.lastname: Wang
authors.forename: Chao
authors.initials: C
authors.lastname: Guo
authors.forename: Yate-Ching
authors.initials: YC
authors.lastname: Yuan
authors.forename: Charles D
authors.initials: CD
authors.lastname: Warden
authors.forename: Marc M
authors.initials: MM
authors.lastname: Baum
mesh_terms: D000328:Adult; D018890:Chemoprevention; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000235:genetics* / Q000517:prevention & control*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D015203:Reproducibility of Results; D014621:Vagina / Q000187:drug effects / Q000378:metabolism*; D055815:Young Adult
chemical_list: D026901:Membrane Transport Proteins