Upregulated Stromal Cell-Derived Factor 1 (SDF-1) Expression and its Interaction With CXCR4 Contribute to the Pathogenesis of Severe Pterygia

Abstract

Stromal cell-derived factor 1 (SDF-1) and its interaction with chemokine receptor 4 (CXCR4) have been noted for participating in the wound healing process, and may paradoxically develop hypertrophic scarring. With viewing pterygia as a product of exaggerated wound formation, we evaluated the effects of SDF-1 and CXCR4 on determining the severity of pterygia. Human pterygial fibroblasts were cultured from excised tissues. Then, expression levels of SDF-1 and CXCR4 were assessed at both the mRNA and protein levels and analyzed with respect to the severity (grade T1 to T3) of pterygia. Expression patterns of SDF-1 and CXCR4 in pterygium tissues were evaluated by immunohistochemistry. Additionally, to investigate the SDF-1-induced myofibroblast transformation of pterygial fibroblasts, the correlation between SDF-1 and α-smooth muscle actin (α-SMA) expression levels was evaluated. Furthermore, α-SMA levels in pterygial fibroblasts were determined before and after knockdown of SDF-1 and blockade of CXCR4 by AMD3100. Stromal cell-derived factor 1 and CXCR4 were expressed in identical areas in severe pterygium tissues (grade T3) and CXCR4-immunopositive cells were concentrated at perivascular regions. Stromal cell-derived factor 1 levels in cultured pterygial fibroblasts correlated positively with the severity of pterygia. Stromal cell-derived factor 1 levels had a significant, positive correlation with α-SMA levels in pterygial fibroblasts. Furthermore, each knockdown of SDF-1 expression and blockade of SDF-1/CXCR4 signaling in severe pterygia significantly reduced α-SMA levels. Stromal cell-derived factor 1 expression is upregulated in severe pterygia, and SDF-1 and CXCR4 interaction may contribute to the myofibroblast transformation, which can be possibly restored through the downregulation of the SDF-1/CXCR4 axis.