Abstract
Purpose:
Biochemical signaling via Stromal cell-derived factor 1 (SDF-1) and its receptor, Chemokine receptor type 4 (CXCR4) had initially attracted attention as a recruiter of progenitor cells to wound for organ repair. Paradoxically, however, SDF-1/CXCR4 signaling is implicated in proliferation and pheno-transdifferentiation of fibroblasts in tumor. With viewing pterygia as exaggerated wound and mimicry of tumor, we investigate the involvement of SDF-1 expression in pathogenesis of pterygia.
Methods:
In cultured stromal fibroblasts of pterygia (74 eyes) and normal conjunctiva (24 eyes), the expression patterns of SDF-1 and CXCR4 were analyzed according to normal or pterygium, recurrency and grade based on pterygial body morphology (T1-T3) or vascularity (V1-V3). To reveal the SDF-1-triggered possible pheno-transdifferentiation of pterygial fibroblasts, the expression of α-SMA, which is the marker of myofibroblasts was co-analyzed paired with SDF-1. Then, the expression level of α-SMA was determined after downregulation of SDF-1 in fibroblasts by siRNA. The mRNA expression was evaluated by RT-PCR, and the proteins were detected by Western blot analysis, immunohisto- and immunocytochemistry.
Results:
Expression of SDF-1 was significantly higher in recurrent, T3 or V3 grade pterygia at both mRNA and protein levels. However, there was no significant difference in CXCR4 expression. In immunohistochemistry, SDF-1 was highly expressed at the stromal layer in recurrent or T3 pterygia, and at perivascular area especially in V3 pterygia. Expression of SDF-1 was positively correlated with that of CXCR4 or α-SMA. Furthermore, the siRNA-SDF-1 reduced the expression level of α-SMA.
Conclusions:
Proliferative gain of function of pterygial fibroblast via SDF-1 expression is possibly associated with pathogenesis of pterygia, especially in determination of recurrence, stromal fleshness and vascularity. This suggests that SDF-1 can be an attractive new therapeutic target to stabilize pterygia proliferation.
Keywords: 665 pterygium •
654 proliferation •
714 signal transduction