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Expression gradient of metalloproteinases and their inhibitors from proximal to distal segments of abdominal aortic aneurysm
Journal of Applied Genetics ( IF 2.0 ) Pub Date : 2021-06-06 , DOI: 10.1007/s13353-021-00642-3
Aleksandra Augusciak-Duma 1 , Karolina L Stepien 1 , Marta Lesiak 1 , Ewa Gutmajster 2 , Agnieszka Fus-Kujawa 1 , Malwina Botor 1 , Aleksander L Sieron 1
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Abdominal aortic aneurysm refers to abnormal, asymmetric distension of the infrarenal aortic wall due to pathological remodelling of the extracellular matrix. The distribution of enzymes remodelling the extracellular matrix and their expression patterns in the affected tissue are largely unknown. The goal of this work was to investigate the expression profiles of 20 selected genes coding for metalloproteinases and their inhibitors in the proximal to the distal direction of the abdominal aortic aneurysm. RNA samples were purified from four lengthwise fragments of aneurysm and border tissue obtained from 29 patients. The quantities of selected mRNAs were determined by real-time PCR to reveal the expression patterns. The genes of interest encode collagenases (MMP1, MMP8, MMP13), gelatinases (MMP2, MMP9), stromelysins (MMP3, MMP7, MMP10, MMP11, MMP12), membrane-type MMPs (MMP14, MMP15, MMP16), tissue inhibitors of metalloproteinases (TIMP1, TIMP2, TIMP3, TIMP4), and ADAMTS proteinases (ADAMTS1, ADAMTS8, and ADAMTS13). It was found that MMP, TIMP, and ADAMTS are expressed in all parts of the aneurysm with different patterns. A developed aneurysm has such a disturbed expression of the main participants in extracellular matrix remodelling that it is difficult to infer the causes of the disorder development. MMP12 secreted by macrophages at the onset of inflammation may initiate extracellular matrix remodelling, which, if not controlled, initiates a feedback loop leading to aneurysm formation.



中文翻译:

金属蛋白酶及其抑制剂从腹主动脉瘤近端到远端的表达梯度

腹主动脉瘤是指由于细胞外基质的病理性重塑导致肾下主动脉壁的异常、不对称扩张。重塑细胞外基质的酶的分布及其在受影响组织中的表达模式在很大程度上是未知的。这项工作的目的是研究 20 个选定的编码金属蛋白酶及其抑制剂的基因在腹主动脉瘤近端至远端方向的表达谱。从 29 名患者获得的动脉瘤和边缘组织的四个纵向片段中纯化 RNA 样品。通过实时 PCR 确定所选 mRNA 的数量以揭示表达模式。感兴趣的基因编码胶原酶(MMP1MMP8MMP13)、明胶酶(MMP2MMP9)、溶基质素(MMP3MMP7MMP10MMP11MMP12)、膜型 MMP(MMP14MMP15MMP16)、金属蛋白酶组织抑制剂(TIMP1TIMP2TIMP3TIMP4)和ADAMTS 蛋白酶(ADAMTS1ADAMTS8ADAMTS13)。发现MMP、TIMP和ADAMTS在动脉瘤的各个部位以不同的模式表达。发达的动脉瘤在细胞外基质重塑中的主要参与者的表达如此紊乱,以至于很难推断出疾病发展的原因。炎症发作时巨噬细胞分泌的MMP12可能会启动细胞外基质重塑,如果不加以控制,则会启动导致动脉瘤形成的反馈回路。

更新日期:2021-06-07
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