Effects of hypoxia on the expression of proangiogenic factors in differentiated 3T3-F442A adipocytes
Effects of hypoxia on the expression of proangiogenic factors in differentiated 3T3-F442A adipocytes
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DOI：
10.1038/sj.ijo.0802407
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发表时间：
2003-10-01
影响因子：
4.9
通讯作者：
Bouloumié, A
中科院分区：
文献类型：
--
作者：
Lolmède, K;de Saint Front, VD;Bouloumié, A
目的：肥胖者脂肪组织生长过程中观察到的脂肪细胞肥大和增生可能促进组织内缺氧区域的出现。本研究的目的是评估缺氧对脂肪细胞衍生的促血管生成因子的表达和分泌的影响。 设计和方法：将分化的3T3-F442A脂肪细胞置于环境缺氧（5％O-2）或通过氯化钴或去铁胺处理化学诱导缺氧。通过明胶酶谱法测定基质金属蛋白酶 2 和 9（MMP-2 和 -9）的活性。通过蛋白质印迹和 RT-PCR 分析来研究血管内皮生长因子 (VEGF)、缺氧诱导因子 1 α (HIF-1α)、瘦素、MMP-2 和 -9 的表达。 结果：低氧压暴露和缺氧模拟治疗与分化的 3T3-F442A 脂肪细胞中葡萄糖消耗和乳酸释放增加相关。它们还导致瘦素、VEGF 和 MMP 表达上调。在缺氧的脂肪细胞核中观察到HIF-1α蛋白的积累增加。结论：缺氧在脂肪细胞中显着增强瘦素、VEGF和MMPs的表达并刺激HIF-1通路。目前的数据表明，缺氧脂肪细胞表达更多的促血管生成因子，并表明缺氧如果发生在脂肪组织中，可能是血管生成过程的调节剂。
OBJECTIVE: Adipocyte hypertrophy combined with hyperplasia, observed during the growth of adipose tissue in obesity, might promote the occurrence of hypoxic areas within the tissue. The aim of the present study is to assess the influence of hypoxia on the expression and secretion of adipocyte-derived proangiogenic factors.DESIGN AND METHODS: Differentiated 3T3-F442A adipocytes were submitted either to ambient hypoxia (5% O-2) or to chemically induced hypoxia by treatments with cobalt chloride or desferrioxamine. The activities of the matrix metalloproteinases 2 and 9 (MMP-2 and -9) were determined by gelatin zymography. The expression of vascular endothelial growth factor (VEGF), hypoxia inducible factor 1 alpha (HIF-1alpha), leptin, MMP-2 and -9 were studied by the use of Western blotting and RT-PCR analyses.RESULTS: Low oxygen pressure exposure and hypoxia mimics treatments were associated with increased glucose consumption and release of lactate in differentiated 3T3-F442A adipocytes. They also led to an upregulation of the expression of leptin, VEGF and MMPs. An enhanced accumulation of HIF-1alpha protein was observed in the hypoxic adipocyte nuclei.CONCLUSION: Hypoxia, in adipocytes, markedly enhances the expression of leptin, VEGF and MMPs and stimulates the HIF-1 pathway. The present data demonstrate that hypoxic adipocytes express more proangiogenic factors and suggest that hypoxia, if occuring in adipose tissue, might be a modulator of the angiogenic process.