Glucose-induced changes in integrins and matrix-related functions in cultured human glomerular epithelial cells
Glucose-induced changes in integrins and matrix-related functions in cultured human glomerular epithelial cells
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DOI：
10.1152/ajprenal.00266.2002
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发表时间：
2003-04-01
影响因子：
4.2
通讯作者：
Tsilibary, EC
中科院分区：
文献类型：
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作者：
Kitsiou, PV;Tzinia, AK;Tsilibary, EC
在培养的人肾小球上皮细胞 (HGEC) 中，25 mM 葡萄糖导致 α(3)-、α(2)- 和 β(1)- 整合素表达减少，而 α(5)- 和 α(v)β(3)-整合素表达增加。这种变化伴随着 HGEC 与 IV 型胶原蛋白结合的减少。在正常 (5 mM) 葡萄糖浓度存在的情况下，细胞与 IV 型胶原蛋白的结合主要由 α(2)β(1) 和 α(5)β(1) 整合素介导，如细胞与 IV 型胶原蛋白粘附通过特异性抗整合素单克隆抗体竞争的实验所示。在高（25 mM）葡萄糖存在下，上调的α(5)-和α(v)β(3)-整合素主要参与细胞与IV型胶原蛋白的结合。此外，高葡萄糖降低了基质金属蛋白酶-2（MMP-2）的表达，这是一种部分受α（3）β（1）-整合素调节的胶原酶，正如针对这些整合素的模拟配体抗体的使用所表明的，这导致培养基中MMP-2的释放量增加。最后，金属蛋白酶-2 组织抑制剂（MMP-2 的特异性抑制剂）在高葡萄糖条件下表达上调，并有助于基质积累。这些变化可能有助于解释糖尿病中的基底膜增厚。
In cultured human glomerular epithelial cells (HGEC), 25 mM glucose resulted in decreased expression of alpha(3)-, alpha(2)-, and beta(1)-integrins and increased expression of alpha(5)- and alpha(v)beta(3)-integrins. This change was accompanied by decreased binding of HGEC to type IV collagen. In the presence of normal (5 mM) glucose concentration, cell binding to type IV collagen was primarily mediated by alpha(2)beta(1)- and alpha(5)beta(1)-integrins, as indicated by experiments in which cell adhesion to type IV collagen was competed by specific anti-integrin monoclonal antibodies. In the presence of high (25 mM) glucose, the upregulated alpha(5)- and alpha(v)beta(3)-integrins were mainly involved in cell binding to type IV collagen. Furthermore, high glucose decreased expression of matrix metalloproteinase-2 (MMP-2), a collagenase regulated in part by alpha(3)beta(1)-integrin, as suggested by the use of ligand-mimicking antibodies against these integrins, which resulted in release of increased amounts of MMP-2 in the culture medium. Finally, tissue inhibitor of metalloproteinase-2, the specific inhibitor of MMP-2, was upregulated in high glucose and could contribute to matrix accumulation. These changes could help explain basement membrane thickening in diabetes.