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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Inhibition of matrix metalloproteinase MMP-2 activates chloride current in human airway epithelial cells.
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Inhibition of matrix metalloproteinase MMP-2 activates chloride current in human airway epithelial cells.

机译：抑制基质金属蛋白酶MMP-2激活人气道上皮细胞中的氯离子电流。

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摘要

Matrix metalloproteinases (MMPs) are involved in the remodeling and degradation of the extracellular matrix. Recently, it has been found that MMPs also contribute to processes not directly related to tissue remodeling, such as platelet aggregation or degranulation of airway gland cells. Since mucus secretion is closely related to ion channel function, we investigated whether MMPs could also be involved in the regulation of ion channels. We used human airway submucosal cell line Calu-3 to study the effects of MMPs on whole-cell current and transepithelial short-circuit current (I(sc)). Phenanthroline, a specific inhibitor of MMPs, increased whole-cell current with the half-maximally effective dose of 5.2 microM, and reversibly activated I(sc) in transepithelial measurements. Current stimulated by phenanthroline displayed linear current-voltage relationships and had inhibitor pharmacology and ion selectivity consistent with cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel activity. Zymography and Western blot showed significant expression of MMP-2 in Calu-3 cells. Moreover, anti-MMP-2 antibodies (1 microg/mL) increased whole-cell current and I(sc), whereas human recombinant MMP-2 (10 ng/mL) reduced it. We also studied the expression of MMPs and the effects of phenanthroline on whole-cell current in A549 cells, which are derived from airway surface epithelium and do not express CFTR Cl- channels. While these cells also showed significant expression of MMP-2, inhibition of this enzyme with phenanthroline exerted no significant effect on whole-cell current. It is concluded that MMP-2 is involved in the regulation of CFTR Cl- channels in human airways.
机译：基质金属蛋白酶（MMPs）参与细胞外基质的重塑和降解。近来，已经发现MMP也促进与组织重塑不直接相关的过程，例如血小板聚集或气道腺细胞脱粒。由于粘液分泌与离子通道功能密切相关，因此我们研究了MMPs是否也可能参与离子通道的调节。我们使用人类气道粘膜下细胞系Calu-3研究了MMP对全细胞电流和跨上皮短路电流（I（sc））的影响。菲咯啉是MMP的特异性抑制剂，在上皮测量中最大半有效剂量为5.2 microM时可增加全细胞电流，并可逆激活I（sc）。菲咯啉刺激的电流表现出线性电流-电压关系，并具有与药性囊性纤维化跨膜电导调节剂（CFTR）Cl通道活性一致的抑制剂药理作用和离子选择性。 Zymography和Western印迹显示在Calu-3细胞中MMP-2明显表达。此外，抗MMP-2抗体（1 microg / mL）增加了全细胞电流和I（sc），而人重组MMP-2（10 ng / mL）降低了它。我们还研究了MMPs的表达以及菲咯啉对A549细胞中全细胞电流的影响，这些细胞来自气道表面上皮细胞，不表达CFTR Cl-通道。尽管这些细胞也显示出MMP-2的显着表达，但是用菲咯啉抑制该酶对全细胞电流没有显着影响。结论是MMP-2参与了人类呼吸道CFTR Cl-通道的调控。

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