TGF-β_2对体外培养的牛眼小梁细胞MMP_2表达和活性的影响

目的了解转化生长因子-β2(TGF-β2)对体外培养的牛眼小梁(TM)细胞基质金属蛋白酶-2(MMP2)的表达和活性的影响,探讨TGF-β2在原发性开角型青光眼(POAG)发病机制中的作用。方法用含有1.0μg/L TGF-β2或含1.0μg/L TGF-β2+100g/L鼠抗人PAI-1IgG(PAI-1中和抗体)的无血清DMEM分别孵育TM细胞24、36、48h。对照组(Co)加入不含实验药物的无血清DMEM,用Western印迹法检测MMP2及纤溶酶原活化抑制剂-1(PAI-1)的表达。结果TGF-β2可显著增强TM细胞MMP2前体及PAI-1的表达。PAI-1中和抗体可促进MMP2前体向其活化形式转化。结论TGF-β2可通过抑制MMP2的活化过程导致TM细胞的细胞外基质(ECM)的异常堆积,造成房水引流阻力的增加,参与POAG的发病。

The effect of TGF-β2 on the expression and activity of MMP2 in cultured bovine trabecular cells

Objective To understand the effect of transforming growth factor-β_(2)(TGF-β_(2)) on the expression and activity of matrix metalloproteinase-2(MMP_(2)) in cultured bovine trabecular cells and to investigate the role of TGF-β_(2) in the pathogenesis of primary open angle glaucoma(POAG). Methods TM cells were incubated in DMEM containing 1.0μg/L TGF-β_(2) or 1.0μg/L TGF-β_(2) with 100mg/L murine monocolonal anti-human PAI-1 IgG or DMEM without any experimental reagent for 24, 36, 48h, respectively. The expression of MMP_(2) or plasminogen activator inhibitor-1(PAI-1) were assayed by Western blot. Results TGF-β_(2 )could enhance the expression of pre-form MMP_(2) and PAI-1. PAI-1 neutralizing antibody could promote transformation of the pre-form MMP_(2) to it's active form. Conclusion TGF-β_(2) can cause the accumulation of ECM in trabecular meshwork by inhibiting the activation process of pre-form MMP_(2), and thus cause the increase of aqueous humor outflow resistance, which contributes to the pathogenesis of POAG.