Upregulation of leptin-receptor in placental cells by Hypoxia
Upregulation of leptin-receptor in placental cells by Hypoxia
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DOI：
10.1016/j.regpep.2010.12.007
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发表时间：
2011-02-25
影响因子：
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通讯作者：
Doetsch, Joerg
中科院分区：
文献类型：
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作者：
Klaffenbach, Daniela;Meissner, Udo;Doetsch, Joerg
目的：瘦素及其受体(Ob-R)在人胎盘中共同表达，提示该激素的自分泌和旁分泌机制。到目前为止，尚不清楚胎盘环境的变化如何影响Ob-R的表达。因此，本研究的主要目的是研究低氧条件下瘦素受体的表达和调控。检测低氧和瘦素对绒毛癌细胞系和原代绒毛滋养层细胞信号转导和细胞增殖的影响。结果：低氧条件下胎盘细胞Leptin受体mRNA和蛋白表达呈时间依赖性诱导。相反，在缺氧条件下，可溶性瘦素受体的表达没有改变。瘦素治疗既不能激活胎盘细胞中的p42/p44，也不能激活胎盘细胞中的STAT3通路，与低氧或常氧条件无关。此外，高浓度的瘦素对胎盘细胞的增殖无影响。结论：低氧可导致胎盘细胞Ob-R表达增加。有趣的是。瘦素依赖的信号转导和增殖仍未受到影响。我们将讨论可溶性瘦素受体在调节游离瘦素水平中的可能作用。(C)2011爱思唯尔B.V.保留所有权利。
Objective: Leptin and its receptor (Ob-R) are co-expressed in human placenta suggesting auto- and paracrine mechanisms of the hormone. So far it is unclear, how changes in the placental environment affect Ob-R expression. Hence, the main purpose of the study was to investigate leptin receptor expression and regulation under hypoxic conditions. The influences of hypoxia and leptin on signal transduction and cell proliferation in chorioncarcinoma cell lines as well as primary villous trophoblasts were determined.Results: We found a time-dependent induction of leptin receptor mRNA and protein in placental cells under hypoxic conditions. In contrast, soluble leptin receptor expression did not change under oxygen deprivation. Leptin treatment neither activated the p42/p44 nor the STAT3 pathway in placental cells, being independent of hypoxic or normoxic conditions. Furthermore, leptin added to the culture medium in high concentrations was unable to interfere with the rate of proliferation.Conclusion: Our data demonstrate that hypoxia leads to an increase of Ob-R expression in placental cells. Interestingly. leptin-dependent signal transduction and proliferation remained unaffected. A possible role of the soluble leptin receptor in modulating free leptin levels will be discussed. (C) 2011 Elsevier B.V. All rights reserved.