Purpose: To identify the candidate genes for pterygia recurrence from a pterygia transcriptome and to analyze their transcriptional regulation and functional relationships.
Methods: Transcriptional networks for pterygia recurrence were constructed using network analysis that was applied to 184 genes that showed a significant twofold change in the whole genome. Of the identified recurrence-related candidate genes in the major networks, periostin and IL-4 were analyzed for transcriptional relationships using pterygia-derived fibroblasts. Immunohistochemical analysis was used to study pterygia tissue. Effector candidate molecule for recurrence periostin was analyzed for cell adhesive function.
Results: The pterygia transcriptome was divided into four major biological networks with high significance scores (P < 10(-17)). The classifier with the highest accuracy using the support vector machine algorithm was periostin, which was successfully linked to the network of cell cycle, connective tissue development and function, and cell morphology. Analyses using pterygia-derived fibroblasts showed that periostin was required for cell adhesion that was mediated by a presumed pterygia-related extracellular matrix protein, fibronectin. Periostin was found to be transcriptionally induced by IL-4. The IL-4-stimulated periostin induction was suppressed by MAP kinase/ERK kinase 1 inhibitor, indicating an involvement of the MAP kinase pathway. Pathologically, IL-4 was transcriptionally elevated in recurrent pterygia tissue and was localized to perivascular tissues and endothelial cells in the stroma of the subconjunctiva of pterygia.
Conclusions: Periostin is induced by IL-4 and is involved in the fibronectin-mediated pterygia fibroblast adhesion. These findings indicate that periostin probably promotes the recurrence of pterygia.