IL-2对视网膜色素上皮细胞外基质合成的影响
Effects of IL-2 on extracellular matrix synthesis in retinal pigment epithelial cells

摘要：目的 探讨炎症因子白介素-2(IL-2)对视网膜色素上皮(RPE)细胞发生上皮间质转分化(EMT)和细胞外基质(ECM)合成的影响。方法 采用10μg/L IL-2诱导RPE细胞，在相应时间点用Real-time PCR和Western blot方法检测EMT特异性指标α-平滑肌肌动蛋白(α-SMA)、ECM主要成分Ⅰ型胶原纤维(COL-1)和纤维连接蛋白(Fn)、转化生长因子β2 (TGF-β2)mRNA及蛋白的表达和JAK/STAT3信号通路的激活。进而用WP1066特异性阻断JAK/STAT3信号通路，观察α-SMA、COL-1、Fn和TGF-β2 mRNA及蛋白的表达变化。结果 RPE细胞经10μg/L IL-2诱导后，Fn、COL-1、TGF-β2 mRNA与蛋白的表达及p-STAT3/STAT3明显增高(P<0.05)，且这种作用随IL-2处理时间增加而增强，而α-SMA mRNA和蛋白表达则无明显变化。JAK/STAT3抑制剂WP1066能有效抑制IL-2诱导的RPE细胞中Fn、COL-1和TGF-β2 mRNA和蛋白的表达。结论 IL-2能通过？？JAK/STAT3？？信号通路促进RPE细胞ECM合成以及TGF-β2的表达，可能在增殖性玻璃体视网膜病变中起重要作用。
ABSTRACT: Objective To determine the effects of interleukin 2 (IL-2) on epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) synthesis in retinal pigment epithelial (RPE) cells. Methods IL-2 of 10μg/L was used to induce RPE cells. Real-time PCR and Western blot methods were used to detect the EMT marker α-smooth muscle actin (α-SMA), the extracellular matrix (ECM) markers fibronectin (Fn) and type I collagen (COL-1), transforming growth factor β2 (TGF-β2), and the activation of the JAK/STAT3 signaling pathway at corresponding time points. Furthermore, JAK/STAT3 signaling pathway was specifically blocked by WP1066, and the changes in α-SMA, COL-1, Fn and TGF-β2 mRNA and protein expressions were detected. Results After induction by 10μg/L of IL-2, the expressions of Fn, COL-1, TGF-β2 mRNA and protein as well as p-STAT3/STAT3 were significantly increased (P<0.05). This effect was correlated with the length of IL-2 treatment, while α-SMA mRNA and protein expression did not change significantly. JAK/STAT3 inhibitor WP1066 could effectively inhibit the expressions of Fn, COL-1 and TGF-β2 in IL-2-induced RPE cells. Conclusion IL-2 promotes ECM synthesis and TGF-β2 expression in RPE cells via JAK/STAT3 signaling pathway, which may play an important role in proliferative vitreoretinopathy.