Miura Shigenori, Shukunami Chisa, Mitsui Kaori, Kondo Jun, Hiraki Yuji
Department of Cellular Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
BMC Cell Biol. 2011 Aug 18;12:34. doi: 10.1186/1471-2121-12-34.
Chondromodulin-I (ChM-I) is an anti-angiogenic glycoprotein that is specifically localized at the extracellular matrix of the avascular mesenchyme including cartilage and cardiac valves. In this study, we characterized the expression pattern of ChM-I during early pregnancy in mice in vivo and its effect on invasion of trophoblastic cells into Matrigel in vitro.
Northern blot analysis clearly indicated that ChM-I transcripts were expressed in the pregnant mouse uterus at 6.5-9.5 days post coitum. In situ hybridization and immunohistochemistry revealed that ChM-I was localized to the mature decidua surrounding the matrix metalloproteinase-9 (MMP-9)-expressing trophoblasts. Consistent with this observation, the expression of ChM-I mRNA was induced in decidualizing endometrial stromal cells in vitro, in response to estradiol and progesterone. Recombinant human ChM-I (rhChM-I) markedly inhibited the invasion through Matrigel as well as the chemotactic migration of rat Rcho-1 trophoblast cells in a manner independent of MMP activation.
This study demonstrates the inhibitory action of ChM-I on trophoblast migration and invasion, implying the potential role of the ChM-I expression in decidual cells for the regulated tissue remodeling and angiogenesis at feto-maternal interface.
软骨调节素-I（ChM-I）是一种抗血管生成糖蛋白，特异性定位于包括软骨和心脏瓣膜在内的无血管间充质的细胞外基质中。在本研究中，我们在体内表征了ChM-I在小鼠妊娠早期的表达模式及其对体外滋养层细胞侵袭基质胶的影响。
Northern印迹分析清楚地表明，ChM-I转录本在交配后6.5 - 9.5天的妊娠小鼠子宫中表达。原位杂交和免疫组织化学显示，ChM-I定位于围绕表达基质金属蛋白酶-9（MMP-9）的滋养层细胞的成熟蜕膜中。与此观察结果一致，体外蜕膜化的子宫内膜基质细胞中，ChM-I mRNA的表达在雌二醇和孕酮的作用下被诱导。重组人ChM-I（rhChM-I）以独立于MMP激活的方式显著抑制大鼠Rcho-1滋养层细胞穿过基质胶的侵袭以及趋化迁移。
本研究证明了ChM-I对滋养层迁移和侵袭的抑制作用，这意味着蜕膜细胞中ChM-I表达在调节母胎界面组织重塑和血管生成中的潜在作用。
