Upregulated Stromal Cell-Derived Factor 1 (SDF-1) Expression and its Interaction With CXCR4 Contribute to the Pathogenesis of Severe Pterygia
Upregulated Stromal Cell-Derived Factor 1 (SDF-1) Expression and its Interaction With CXCR4 Contribute to the Pathogenesis of Severe Pterygia
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DOI：
10.1167/iovs.13-13044
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发表时间：
2013-11-01
影响因子：
4.4
通讯作者：
Kim, Jae Chan
中科院分区：
文献类型：
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作者：
Kim, Kyoung Woo;Park, Soo Hyun;Kim, Jae Chan
目的。基质细胞衍生因子 1 (SDF-1) 及其与趋化因子受体 4 (CXCR4) 的相互作用已被注意到参与伤口愈合过程，并且可能矛盾地形成肥厚性疤痕。将翼状胬肉视为夸大伤口形成的产物，我们评估了 SDF-1 和 CXCR4 在确定翼状胬肉严重程度方面的作用。方法。从切除的组织中培养人翼状胬肉成纤维细胞。然后，在 mRNA 和蛋白质水平上评估 SDF-1 和 CXCR4 的表达水平，并分析翼状胬肉的严重程度（T1 至 T3 级）。通过免疫组织化学评估翼状胬肉组织中 SDF-1 和 CXCR4 的表达模式。此外，为了研究 SDF-1 诱导的翼状胬肉成纤维细胞的肌成纤维细胞转化，评估了 SDF-1 和 α-平滑肌肌动蛋白 (α-SMA) 表达水平之间的相关性。此外，在AMD3100敲低SDF-1和阻断CXCR4之前和之后测定了翼状胬肉成纤维细胞中的α-SMA水平。 结果。基质细胞衍生因子1和CXCR4在严重翼状胬肉组织（T3级）的相同区域表达，并且CXCR4免疫阳性细胞集中在血管周围区域。培养的翼状胬肉成纤维细胞中基质细胞衍生因子 1 的水平与翼状胬肉的严重程度呈正相关。基质细胞衍生因子 1 水平与翼状胬肉成纤维细胞中的 α-SMA 水平呈显着正相关。此外，在严重翼状胬肉中，每次敲低 SDF-1 表达和阻断 SDF-1/CXCR4 信号传导都会显着降低 α-SMA 水平。 结论。严重翼状胬肉中基质细胞衍生因子 1 表达上调，SDF-1 和 CXCR4 相互作用可能有助于肌成纤维细胞转化，而肌成纤维细胞转化可能通过 SDF-1/CXCR4 轴的下调而恢复。
PURPOSE. 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.METHODS. 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 alpha-smooth muscle actin (alpha-SMA) expression levels was evaluated. Furthermore, alpha-SMA levels in pterygial fibroblasts were determined before and after knockdown of SDF-1 and blockade of CXCR4 by AMD3100.RESULTS. 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 alpha-SMA levels in pterygial fibroblasts. Furthermore, each knockdown of SDF-1 expression and blockade of SDF-1/CXCR4 signaling in severe pterygia significantly reduced alpha-SMA levels.CONCLUSIONS. 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.