Activation of MAPK Signaling Pathway and NF-B in Primary Pterygium Specimens Correlate With Clinical Parameters

Abstract

Purpose: : Involvement of signaling pathway of mitogen-activated protein kinases (MAPK) and nuclear factor-ΚB (NF-ΚB) activation has been reported in pterygium. We previously demonstrated that: 1) JNK was more activated in primary pterygium specimens (PP) and ipsilateral pterygium-free conjunctiva biopsies (PFC) than in healthy conjunctiva biopsies (HC), and 2) IΚBα was more activated in PFC than in HC. The aim of this study was to determine if there was any correlation between the levels of those molecules and between them and clinical parameters.

Methods: : The total (t) and phosphorylated (p) levels of ERK1/2, p38 JNK MAPK, and IΚB-α levels were analyzed in three types of samples: PP (n=21), PFC (n=8) and HC (n=5). To study potential correlation among the levels of those molecules Spearman’s Rho coefficient was used. Additionally, correlations between molecule levels and demographic characteristics, size of pterygium head, and pterygium grade were performed by Mann-Whitney U test or Kruskal-Wallis Anova test with Dunn's multiple comparison post-test.

Results: : Significant positive correlations among protein levels were as follows: 1) HC: t-ERK1/2 with t-IΚB-α. 2) PFC: t-ERK1/2 with t-IΚB-α, t-p38, and t-JNK; t-p38 with t-IΚB-α; p/t-p38 with p/t-ERK1/2. 3) PP: p-JNK with p-ERK1/2 and p-p38; t-p38 with t-ERK1/2, t-JNK, and t-IΚB-α; t-JKN with t-ERK1/2 and t-IΚB-α; p/t-JNK with p/t-ERK1/2 and t-p38. Patients who were born or had lived near the equator more than 50% of their life showed significantly decreased p-ERK1/2, p-JNK, t-p38, and t-JNK levels, and increased levels of p/t-p38. The size of pterygium head correlated positively with p-ERK1/2, p/t-ERK1/2, t-IkB-α, t-p38 and t-JNK, but correlated negatively with p/t-p38. Finally, PP grade 3 had significantly decreased levels of t-ERK1/2 and increased levels of p/t-ERK1/2 compared with less severe grades.

Conclusions: : These findings support the assumption that the inflammatory component in pterygium pathogenesis may have clinical relevance and open potential therapeutic interventions.

Keywords: pterygium • inflammation • conjunctiva