Mast cell degranulation in rat uterine cervix during pregnancy correlates with expression of vascular endothelial growth factor mRNA and angiogenesis
Mast cell degranulation in rat uterine cervix during pregnancy correlates with expression of vascular endothelial growth factor mRNA and angiogenesis
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DOI：
10.1530/rep-06-0168
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发表时间：
2007-05-01
期刊：
影响因子：
3.8
通讯作者：
Luque, E. H.
中科院分区：
文献类型：
--
作者：
Bosquiazzo, V. L.;Ramos, J. G.;Luque, E. H.
妊娠期间子宫颈血管生长与肥大细胞（MC）脱颗粒有关。为了更好地了解这一过程的机制，我们解剖了完整妊娠大鼠的子宫，用溴脱氧尿苷掺入技术测量了内皮细胞的增殖。RT-PCR检测血管内皮生长因子（VEGF） mRNA总表达量和VEGF剪接变异的相对丰度（120,164和188）。免疫组织化学检测VEGF蛋白表达。为了研究MCs对颈椎血管生成的作用，第二组怀孕动物被注射MCs稳定剂（cromoglyate二钠）来抑制MCs脱粒。采用RIA法测定血清中17种β -雌二醇（E-2）水平。在完整妊娠大鼠中，VEGF mRNA表达与内皮细胞增殖和循环E-2水平呈正相关。检测到所有选择的VEGF基因剪接变体，其相对丰度在整个妊娠期间没有任何变化。与对照组相比，经甘草酸二钠处理的动物内皮细胞增殖和VEGF mRNA表达均下降。VEGF mRNA剪接变异体的相对丰度和血清E-2水平在各实验组之间无显著差异。这些结果表明，完整妊娠大鼠子宫颈中VEGF mRNA表达与E-2血清水平存在时间依赖性，而MC稳定剂处理的动物降低了VEGF表达，但不改变E-2血清水平。我们认为妊娠期间宫颈血管生成可能受到内源性E-2和MC颗粒中储存的化学介质通过vegf依赖途径的调节机制。
Vascular growth of the uterine cervix during pregnancy is associated with mast cell (MC) degranulation. To better understand the mechanism underlying this process, uterine cervices of intact pregnant rats were dissected and endothelial cell proliferation was measured by a bromodeoxyuridine incorporation technique. Total vascular endothelial growth factor (VEGF) mRNA expression and the relative abundance of VEGF splice variants (120,164, and 188) were determined by RT-PCR. VEGF protein expression was evaluated by immunohistochernistry. To investigate the role of MCs on cervical angiogenesis, a second set of pregnant animals were treated with an MC stabilizer (disodium cromoglycate) to inhibit MC degranulation. Furthermore, 17 beta-estradiol (E-2) serum levels were established by RIA. In intact pregnant rats, VEGF mRNA expression was positively correlated with endothelial cell proliferation and circulating E-2 levels. All selected splice variants of VEGF gene were detected and their relative abundance did not show any change throughout pregnancy. Animals treated with disodium cromoglycate showed a decrease in endothelial cell proliferation and in VEGF mRNA expression compared with controls. Relative abundance of VEGF mRNA splice variants and E-2 serum levels showed no differences between these experimental groups. These results show a time-dependent correlation between VEGF mRNA expression and E-2 serum levels in the uterine cervix of intact pregnant rats, while MC stabilizer-treated animals reduced the VEGF expression without modifying E-2 serum levels. We suggest that cervical angiogenesis during pregnancy could be regulated by a mechanism which involves endogenous E-2 and chemical mediators stored in MC granules via a VEGF-dependent pathway.