Slit2 Overexpression Results in Increased Microvessel Density and Lesion Size in Mice With Induced Endometriosis
Slit2 Overexpression Results in Increased Microvessel Density and Lesion Size in Mice With Induced Endometriosis
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DOI：
10.1177/1933719112452940
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发表时间：
2013-03-01
影响因子：
2.9
通讯作者：
Geng, Jian-Guo
中科院分区：
文献类型：
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作者：
Guo, Sun-Wei;Zheng, Yu;Geng, Jian-Guo
我们最近报道，Slit/Roundabout（ROBO）1通路可能是子宫内膜异位症复发的组成生物标志物，可能通过促进血管生成。在这项研究中，我们试图确定Slit 2过表达是否可以促进血管生成，增加病变大小，并诱导痛觉过敏诱导子宫内膜异位症小鼠。我们使用了30只Slit 2转基因（S）和29只野生型（W）小鼠，并将子宫内膜碎片从S交叉移植到W（SW组），反之亦然（WS组），以及S和W（分别为SS和WW组）内的子宫内膜碎片交叉移植到腹膜腔中，诱导子宫内膜异位症。我们还在S和W小鼠（分别为Sm和Wm组）中进行了假手术。然后评价异位植入物的大小、微血管密度（MVD）和对ROBO 1的免疫反应性，以及异位和在位子宫内膜中的血管内皮细胞生长因子（VEGF），沿着所有小鼠的热板和甩尾试验。我们发现，子宫内膜异位症的诱导导致全身性痛觉过敏，这是不受Slit 2过表达。Slit 2过表达增加了异位内膜和在位内膜中的病灶大小，并与MVD呈正相关。在异位内膜中，Slit 2表达水平似乎与MVD相关，但与VEGF免疫反应性无关。因此，我们得出结论，Slit 2可能在子宫内膜异位症的血管生成中发挥重要作用。血管生成的增加，如测量的MVD，但不是VEGF免疫反应，可能会导致增加病变大小诱导子宫内膜异位症。因此，SLIT 2/ROBO 1通路可能成为治疗子宫内膜异位症的潜在靶点。
We recently reported that Slit/Roundabout (ROBO) 1 pathway may be a constituent biomarker for recurrence of endometriosis, likely through promoting angiogenesis. In this study, we sought to determine as whether Slit2 overexpression can facilitate angiogenesis, increase lesion size, and induce hyperalgesia in mice with induced endometriosis. We used 30 Slit2 transgenic (S) and 29 wild-type (W) mice and cross-transplanted endometrial fragments from S to W (group SW) and vice versa (group WS), and also within the S and W (groups SS and WW, respectively), into the peritoneal cavity, inducing endometriosis. We also performed a sham surgery within both S and W mice (groups Sm and Wm, respectively). The size of the ectopic implants, microvessel density (MVD) and immunoreactivity to ROBO1, and vascular endothelial cell growth factor (VEGF) in ectopic and eutopic endometrium, along with hotplate and tail-flick tests in all mice, were then evaluated. We found that the induction of endometriosis resulted in generalized hyperalgesia, which was unaffected by Slit2 overexpression. Slit2 overexpression did increase the lesion size significantly and correlated positively with the MVD in ectopic and eutopic endometrium. Slit2 expression levels appear to correlate with the MVD, but not with VEGF immunoreactivity, in ectopic endometrium. Consequently, we conclude that Slit2 may play an important role in angiogenesis in endometriosis. The increased angiogenesis, as measured by MVD, but not VEGF immunoreactivity, likely resulted in increased lesion size in induced endometriosis. Thus, SLIT2/ROBO1 pathway may be a potential therapeutic target for treating endometriosis.