Expression and activation of MMP-2,-3,-9,-14 are induced in rat colon after abdominal X-irradiation
Expression and activation of MMP-2,-3,-9,-14 are induced in rat colon after abdominal X-irradiation
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DOI：
10.1080/00365520510023963
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发表时间：
2006-01-01
影响因子：
1.9
通讯作者：
Mathe, D
中科院分区：
文献类型：
--
作者：
Strup-Perrot, C;Vozenin-Brotons, MC;Mathe, D
Objective.结肠对单剂量辐射的反应的特征是上皮剥脱，然后恢复。细胞外基质（ECM）重塑参与这两个阶段。本研究的目的是描述基质金属蛋白酶（MMPs）及其刺激和抑制途径在辐射诱导的结肠组织ECM重塑中的作用。材料和方法。用单剂量10戈伊X射线照射大鼠腹部。采用酶谱法、免疫组化和实时逆转录-聚合酶链反应（RT-PCR）等方法，分析了放射后1、3和7天远端结肠中MMPs和参与其激活和抑制的分子（纤溶酶/纤溶酶原; TIMPs）、炎症介质（IL-1 β、TNF-α）的活性、定位和mRNA水平。结果本研究的主要发现是，辐射诱导的粘膜结构改变伴随着参与基底膜降解的MMP亚型（MMP-2、MMP-3和MMP-9）的局部表达和活化增加。我们研究了MMP-2激活途径，发现可溶性炎症介质（TNF-α和IL-1 β）的mRNA水平早期增加。此外，发现MMP-2激活分子（如MMP-14）和纤溶酶原/纤溶酶系统中涉及的分子的转录和活性在剥脱阶段增加。有趣的是，在恢复期观察到MMP抑制剂TIMP-1和派-1的诱导。MMP抑制剂可能能够通过抑制ECM降解来停止急性伤口愈合反应。结论.这项研究为暴露于电离辐射后结肠ECM重塑带来了新的见解，并突出了MMP亚型在基底膜降解中的作用。
Objective. Colonic response to single-dose irradiation is characterized by epithelial denudation followed by restitution. Extracellular matrix (ECM) remodeling is involved in both of these phases. The aim of this study was to characterize the contribution of matrix metalloproteinases (MMPs) and of their stimulatory and inhibitory pathways in radiation-induced ECM remodeling in colonic tissue. Material and methods. Rats were irradiated with single-dose 10 Gy X-rays to the abdomen. Activity, localization, and mRNA levels of MMPs and molecules involved in their activation and inhibition (plasmin/plasminogen; TIMPs), of inflammatory mediators (IL-1 beta, TNF-alpha) in the distal colon, 1, 3, and 7 days after irradiation were analyzed using a combination of approaches including zymography, immunohistochemistry, and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Results. The main finding of this study is that radiation-induced alteration of the mucosal structure is concomitant with local increased expression and activation of MMP subtypes involved in basement membrane degradation (MMP-2, -3, and -9). We investigated MMP-2 activation pathways and found an early increase in mRNA levels of soluble inflammatory mediators (TNF-alpha and IL-1 beta). Furthermore, transcription and activity of MMP-2 activating molecules, such as MMP-14, and molecules involved in the plasminogen/plasmin system were found to increase during the denudation phase. Interestingly, induction of MMP inhibitors TIMP-1 and PAI-1 was observed during the restitution phase. MMP inhibitors may be able to stop acute wound healing response by inhibiting ECM degradation. Conclusions. This study brings new insights into ECM remodeling in the colon after exposure to ionizing radiation and highlights the role of MMP subtypes specialized in basement membrane degradation.