Activation of MAPK Signaling Pathway and NF-kappa B Activation in Pterygium and Ipsilateral Pterygium-Free Conjunctival Specimens

作者：Torres Jenice; Enriquez de Salamanca Amalia^*; Fernandez Itziar; Teresa Rodriguez Ares Maria; Quadrado Maria J; Murta Joaquim; Benitez del Castillo Jose M; Stern Michael E; Calonge Margarita

来源：Investigative Ophthalmology & Visual Science, 2011, 52(8): 5842-5852.

DOI：10.1167/iovs.10-6673

PURPOSE. To evaluate mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-kappa B) 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-kappa B inhibitor-alpha (I kappa B-alpha) 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 I kappa B-alpha levels than did healthy conjunctivas. Decreased total JNK and I kappa B-alpha and increased phospho-I kappa B-alpha levels and phospho/total ratio of JNK and I kappa B-alpha 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-kappa B 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 I kappa B-alpha suggests these molecules as potential biomarkers of inflammation in pterygia. (Invest Ophthalmol Vis Sci. 2011;52:5842-5852) DOI: 10.1167/iovs.10-6673

• 出版日期2011-7