High Glucose and Advanced Glycation End Products Induce CD147-Mediated MMP Activity in Human Adipocytes.
High Glucose and Advanced Glycation End Products Induce CD147-Mediated MMP Activity in Human Adipocytes.
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作者：
Mahmoud AM;Ali MM
Basigin（CD 147）是一种跨膜糖蛋白，其调节多种生理过程，包括基质金属蛋白酶（MMPs）的产生和活性。CD 147的活性主要取决于其糖基化，其在病理生理条件之间变化。然而，它是未知的，是否CD 147活性或其在MMP调节功能的糖尿病环境，其特征是高葡萄糖（HG）水平和过量的糖化终产物（AGEs）的影响。在这项研究中，我们研究了HG和AGEs对人脂肪细胞CD 147表达的影响。并探讨了核因子κ B（NFκB）和AGE受体（AGEs）在这一过程中的介导作用。我们的研究结果表明，羧甲基赖氨酸和HG增加CD 147的表达和糖基化，这是伴随着MMP 2和MMP 9的表达和活性的增加，以及N-乙酰葡糖胺转移酶，MGAT 5的上调。这些作用可通过NFκB和RAGE抑制、CD 147基因沉默以及糖基化抑制剂衣霉素消除。总之，目前的研究结果表明AGEs和HG诱导脂肪细胞中CD 147的表达和糖基化，NFκB和RAGE可能介导。这一途径的关键结果之一是增加MMP活性，已知其有助于糖尿病的心血管并发症。
Basigin (CD147) is a transmembrane glycoprotein that regulates several physiological processes, including the production and activity of matrix metalloproteinases (MMPs). The activity of CD147 depends mainly on its glycosylation, which varies among pathophysiological conditions. However, it is unknown whether CD147 activity or its function in MMP regulation are affected by the diabetic environment, which is characterized by high glucose (HG) levels and an excess of glycation end products (AGEs). In this study, we investigated the effect of HG and AGEs on CD147 expression in human adipocytes. We also examined the mediating role of nuclear factor kappa B (NFκB) and receptor of AGE (RAGE) to this effect. Our findings show that carboxymethyl lysine and HG increased CD147 expression and glycosylation, which was accompanied by increases in MMP2 and MMP9 expression and activity, as well as upregulations of the N-acetylglucosaminyltransferase, MGAT5. These effects were abolished by NFκB and RAGE inhibition, CD147 gene silencing, and by the glycosylation inhibitor, tunicamycin. In conclusion, the current findings indicate that AGEs and HG induce CD147 expression and glycosylation in adipocytes, with possible mediation by NFκB and RAGE. One of the critical outcomes of this pathway is augmented MMP activity known to contribute to cardiovascular complications in diabetes.
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影响因子：
4
作者：
Grass GD;Toole BP
通讯作者：
Toole BP
AGE-RAGE 信号生成特定的 NF-κB RelA“条形码”，指导 I 型胶原蛋白的表达。
影响因子：
4.6
作者：
Peng Y;Kim JM;Park HS;Yang A;Islam C;Lakatta EG;Lin L
通讯作者：
Lin L
影响因子：
9.3
作者：
Newby, Andrew C.
通讯作者：
Newby, Andrew C.
影响因子：
11.4
作者：
Ott, Christiane;Jacobs, Kathleen;Haucke, Elisa;Santos, Anne Navarrete;Grune, Tilman;Simm, Andreas
通讯作者：
Simm, Andreas
影响因子：
6.1
作者：
Chang, Chiz-Tzung;Wu, Mai-Szu;Yang, Chih-Wei
通讯作者：
Yang, Chih-Wei