MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Differentiation. 2010 Sep-Oct;80(2-3):89-98. doi: 10.1016/j.diff.2010.06.003. Epub 2010 Jul 15.
Paracrine signalling from mesenchyme to epithelium plays a key role in regulating prostate organogenesis and it is important to identify the mesenchymally expressed molecules that regulate organ growth, though currently few such molecules are known. Tyrosine kinase signalling via EphB receptors has been characterised in many developmental processes, and EphB3 mRNA expression was detected in prostate inductive mesenchyme in previous gene profiling studies. This led us to examine the expression and function of EphrinB signalling in prostate development, to determine if EphrinB ligands might function as mesenchymal paracrine regulators of prostate growth. Using PCR, wholemount in situ hybridisation, and immunohistochemistry we examined the expression of EphB receptors and EphrinB ligands in rat prostate during development to determine which showed mesenchymal expression. EphB3 and EphrinB1 transcripts and proteins were expressed in the mesenchyme of developing prostate and in female urogenital mesenchyme and smooth muscle. The function of EphrinB signalling was examined using in vitro organ culture assays of ventral prostate (VP), which were treated with EphB3-Fc and EphrinB1-Fc proteins to inhibit or augment Ephrin signalling. Addition of recombinant EphB3-Fc resulted in a significant decrease in VP organ size, while recombinant EphrinB1-Fc resulted in a significant increase in VP organ size and epithelial proliferation. Additionally, EphrinB1-Fc reduced the degree of epithelial branching in VP organs and increased ductal tip size, though without disrupting normal differentiation. We have identified expression of EphrinB1 in prostatic mesenchyme and suggest that the EphrinB signalling system acts as a regulator of prostate growth. EphrinB-EphB signalling may function as an autocrine regulator of mesenchyme and/or as a paracrine regulator of epithelia.
旁分泌信号从间充质到上皮在调节前列腺器官发生中起着关键作用，识别调节器官生长的间充质表达分子很重要，尽管目前已知的此类分子很少。EphB 受体的酪氨酸激酶信号在许多发育过程中都得到了描述，并且在前基因图谱研究中检测到前列腺诱导间充质中 EphB3 mRNA 的表达。这促使我们研究 EphrinB 信号在前列腺发育中的表达和功能，以确定 EphrinB 配体是否可能作为前列腺生长的间质旁分泌调节剂发挥作用。我们使用 PCR、整体原位杂交和免疫组织化学技术，检查了 EphB 受体和 EphrinB 配体在大鼠前列腺发育过程中的表达，以确定哪些显示出间充质表达。EphB3 和 EphrinB1 转录本和蛋白质在发育中的前列腺间质以及女性泌尿生殖间质和平滑肌中表达。使用 EphB3-Fc 和 EphrinB1-Fc 蛋白处理体外器官培养的腹侧前列腺 (VP)，以抑制或增强 Ephrin 信号，从而检查 EphrinB 信号的功能。添加重组 EphB3-Fc 导致 VP 器官大小显著减小，而重组 EphrinB1-Fc 导致 VP 器官大小和上皮增殖显著增加。此外，EphrinB1-Fc 减少了 VP 器官上皮分支的程度，并增加了导管尖端的大小，尽管没有破坏正常分化。我们已经确定 EphrinB1 在前列腺间质中的表达，并提出 EphrinB 信号系统是前列腺生长的调节剂。EphrinB-EphB 信号可能作为间充质的自分泌调节剂和/或作为上皮的旁分泌调节剂发挥作用。
