title: The monocarboxylate transporter inhibitor α-cyano-4-hydroxycinnamic acid disrupts rat lung branching.
abstract: OBJECTIVE
  The human embryo develops in a hypoxic environment. In this way, cells have to rely on the glycolytic pathway for energy supply, leading to an intracellular accumulation of monocarboxylates such as lactate and pyruvate. These acids have an important role in cell metabolism and their rapid transport across the plasma membrane is crucial for the maintenance of intracellular pH homeostasis. This transport is mediated by a family of transporters, designated by monocarboxylate transporters (MCTs), namely isoforms 1 and 4. MCT1/4 expression is regulated by the ancillary protein CD147.The general aim of this study was to characterize the expression pattern of MCT1/4, CD147 and the glucose transporter GLUT1 during human fetal lung development and elucidate the role of MCTs in lung development.
  
  
  METHODS
  The expression pattern of MCT1/4 and GLUT1 was characterized by immunohistochemistry and fetal lung viability and branching were evaluated by exposing rat fetal lung explants to CHC, an inhibitor of MCT activity.
  
  
  RESULTS
  Our findings show that all the biomarkers are differently expressed during fetal lung development and that CHC appears to have an inhibitory effect on lung branching and viability, in a dose dependent way.
  
  
  CONCLUSIONS
  We provide evidence for the role of MCTs in embryo lung development, however to prove the dependence of MCT activity further studies are waranted.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Granja
authors.forename: Filipa
authors.initials: F
authors.lastname: Morais-Santos
authors.forename: Vera
authors.initials: V
authors.lastname: Miranda-Gonçalves
authors.forename: Manuel
authors.initials: M
authors.lastname: Viana-Ferreira
authors.forename: Rosete
authors.initials: R
authors.lastname: Nogueira
authors.forename: Cristina
authors.initials: C
authors.lastname: Nogueira-Silva
authors.forename: Jorge
authors.initials: J
authors.lastname: Correia-Pinto
authors.forename: Fátima
authors.initials: F
authors.lastname: Baltazar
mesh_terms: D000818:Animals; D051926:Basigin / Q000378:metabolism; D002478:Cells, Cultured; D003373:Coumaric Acids / Q000494:pharmacology*; D047108:Embryonic Development / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D051926:Basigin; D003373:Coumaric Acids; D051272:Glucose Transporter Type 1; D027501:Monocarboxylic Acid Transporters; D020033:Protein Isoforms; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C007175:alpha-cyano-4-hydroxycinnamate