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首页> 外文期刊>American Journal of Physiology >Transforming growth factor-beta1 increases airway wound repair via MMP-2 upregulation: a new pathway for epithelial wound repair?
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Transforming growth factor-beta1 increases airway wound repair via MMP-2 upregulation: a new pathway for epithelial wound repair?

机译：转化生长因子-beta1通过MMP-2上调增加气道伤口修复：上皮伤口修复的新途径吗？

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摘要

In vivo, transforming growth factor (TGF)-beta1 and matrix metalloproteinases (MMPs) present at the site of airway injury are thought to contribute to epithelial wound repair. As TGF-beta1 can modulate MMP expression and MMPs play an important role in wound repair, we hypothesized that TGF-beta1 may enhance airway epithelial repair via MMPs secreted by epithelial cells. We evaluated the in vitro influence of TGF-beta1 on wound repair in human airway epithelial cells cultured under conditions allowing differentiation. The results showed that TGF-beta1 accelerated in vitro airway wound repair, whereas MMP inhibitors prevented this acceleration. In parallel, we examined the effect of TGF-beta1 on the expression of MMP-2 and MMP-9. TGF-beta1 induced a dramatic increase of MMP-2 expression with an increased steady-state level of MMP-2 mRNA, contrasting with a slight increase in MMP-9 expression. To confirm the role of MMP-2, we subsequently evaluated the effect of MMP-2 on in vitro airway wound repair and demonstrated that the addition of MMP-2 reproduced the acceleration of wound repair induced by TGF-beta1. These results strongly suggest that TGF-beta1 increases in vitro airway wound repair via MMP-2 upregulation. It also raises the issue of a different in vivo biological role of MMP-2 and MMP-9 depending on the cytokine microenvironment.
机译：在体内，存在于气道损伤部位的转化生长因子（TGF）-β1和基质金属蛋白酶（MMP）被认为有助于上皮伤口的修复。由于TGF-beta1可以调节MMP的表达，并且MMP在伤口修复中起重要作用，因此我们假设TGF-beta1可能通过上皮细胞分泌的MMP增强气道上皮修复。我们评估了TGF-β1对在允许分化条件下培养的人气道上皮细胞伤口修复的体外影响。结果表明，TGF-β1加速了体外气道伤口修复，而MMP抑制剂阻止了这种加速。平行地，我们检查了TGF-β1对MMP-2和MMP-9表达的影响。 TGF-beta1诱导MMP-2表达的急剧增加，并增加了MMP-2 mRNA的稳态水平，而MMP-9表达则略有增加。为了确认MMP-2的作用，我们随后评估了MMP-2对体外气道伤口修复的作用，并证明了MMP-2的添加可重现TGF-beta1诱导的伤口修复。这些结果强烈表明，TGF-β1通过MMP-2上调增加体外气道伤口修复。它还提出了取决于细胞因子微环境的MMP-2和MMP-9在体内生物学作用不同的问题。

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