title: Activation of MAPK signaling pathway and NF-kappaB activation in pterygium and ipsilateral pterygium-free conjunctival specimens.
abstract: OBJECTIVE
  To evaluate mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) signaling pathways in pterygium and pterygium-free conjunctivas.
  
  
  METHODS
  Primary pterygia (n = 21), ipsilateral superior-temporal bulbar conjunctivas (n = 8), and healthy conjunctival (n = 5) biopsy specimens were analyzed. Total and phosphorylated (phospho) levels of extracellular-regulated 1/2 (ERK1/2), p38, and c-jun N-terminal (JNK) MAPKs and NF-κB inhibitor-alpha (IκΒ-α) were analyzed by immunobead-based assay. Tissue phospho-, total protein, and activation values determined by phospho/total ratios were compared. Correlation among those values and clinical parameters were determined. Average-linkage hierarchical cluster analysis identified patients with similar protein activation values. The k-nearest neighbor classifier predicted the origin of specimens based on protein levels.
  
  
  RESULTS
  Pterygium samples had significantly lower total JNK and IκΒ-α levels than did healthy conjunctivas. Decreased total JNK and IκΒ-α and increased phospho-IκΒ-α levels and phospho/total ratio of JNK and IκΒ-α were present in ipsilateral conjunctivas compared with healthy conjunctivas. Protein levels were correlated among them in pterygium, ipsilateral, and healthy conjunctivas and with sun exposure, pterygium grade, and pterygium measurements. Cluster analysis of activation values and ratios in pterygium and ipsilateral-conjunctiva revealed different groups of patients with similar values. Prediction accuracy was 70% to 80% for the classifiers phospho- and total protein levels and phospho/total ratio.
  
  
  CONCLUSIONS
  Pterygium and pterygium-free ipsilateral conjunctivas had alterations in MAPK and NF-κB pathways not present in healthy conjunctivas. The high prediction accuracy based on phospho- and total protein levels and phospho/total ratio of ERK1/2, p38, JNK, and IκB-α suggests these molecules as potential biomarkers of inflammation in pterygia.
authors.affiliation: IOBA, University of Valladolid, Valladolid, Spain;
authors.forename: Jenice
authors.initials: J
authors.lastname: Torres
authors.forename: Amalia
authors.initials: A
authors.lastname: Enríquez-de-Salamanca
authors.forename: Itziar
authors.initials: I
authors.lastname: Fernández
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Rodríguez-Ares
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Quadrado
authors.forename: Joaquim
authors.initials: J
authors.lastname: Murta
authors.forename: José M
authors.initials: JM
authors.lastname: Benítez del Castillo
authors.forename: Michael E
authors.initials: ME
authors.lastname: Stern
authors.forename: Margarita
authors.initials: M
authors.lastname: Calonge
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001706:Biopsy; D003228:Conjunctiva / Q000166:cytology / Q000201:enzymology*; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011237:Predictive Value of Tests; D011625:Pterygium / Q000201:enzymology* / Q000473:pathology*; D013472:Sunlight; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D048031:JNK Mitogen-Activated Protein Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases