Institute of Cell Biology, Histology and Embryology, Center for Molecular Medicine, Medical University of Graz, Harrachgasse 21/7, 8010 Graz, Austria.
Histochem Cell Biol. 2011 Feb;135(2):203-13. doi: 10.1007/s00418-011-0784-4. Epub 2011 Feb 3.
Fibulin-5 is a secreted extracellular matrix glycoprotein and displays a diverse panel of biological functions, which can be segregated into elastogenic as well as extra-elastogenic functions. While elastogenic functions of fibulin-5 include essential roles in early steps of elastic fibre assembly, extra-elastogenic functions are widespread. Depending on the cell type used, fibulin-5 mediates cell adherence via a subset of integrins, antagonizes angiogenesis and inhibits migration as well as proliferation of endothelial and smooth muscle cells. In this study, we focused on the spatiotemporal expression of fibulin-5 in the human placenta. With progressing gestation, placental fibulin-5 expression increased from first trimester towards term. At term, placental fibulin-5 mRNA expression is lower when compared with other well-vascularized organs such as lung, kidney, heart, uterus and testis. In first trimester, placenta immunohistochemistry localized fibulin-5 in villous cytotrophoblasts and extravillous cytotrophoblasts of the proximal cell column. In term placenta, fibulin-5 was detected in the endothelial basement membrane and adventitia-like regions of vessels in the chorionic plate and stem villi. Cell culture experiments with the villous trophoblast-derived cell line BeWo showed that fibulin-5 expression was downregulated during functional differentiation and intercellular fusion. Moreover, cultivation of BeWo cells under low oxygen conditions impaired intercellular fusion and upregulated fibulin-5 expression. The spatiotemporal shift from the trophoblast compartment in first trimester to the villous vasculature at term suggests a dual role of fibulin-5 in human placental development.
纤连蛋白-5 是一种分泌型细胞外基质糖蛋白，具有多种生物学功能，可分为弹性原性和非弹性原性功能。虽然纤连蛋白-5 的弹性原性功能包括在弹性纤维组装的早期步骤中发挥重要作用，但非弹性原性功能却广泛存在。根据所使用的细胞类型，纤连蛋白-5 通过一组整合素介导细胞黏附，拮抗血管生成，并抑制内皮细胞和平滑肌细胞的迁移和增殖。在本研究中，我们专注于纤连蛋白-5 在人胎盘中的时空表达。随着妊娠的进展，胎盘纤连蛋白-5 的表达从早孕期向足月期增加。在足月时，与其他血管丰富的器官（如肺、肾、心、子宫和睾丸）相比，胎盘纤连蛋白-5 mRNA 的表达较低。在早孕期，胎盘免疫组织化学将纤连蛋白-5 定位于绒毛滋养层细胞和近细胞柱的绒毛外滋养层细胞。在足月胎盘中，纤连蛋白-5 被检测到在绒毛板和干绒毛中的血管内皮基膜和类似外膜的区域。用绒毛滋养层衍生的细胞系 BeWo 进行的细胞培养实验表明，纤连蛋白-5 的表达在功能分化和细胞间融合过程中下调。此外，在低氧条件下培养 BeWo 细胞会损害细胞间融合并上调纤连蛋白-5 的表达。从早孕期的滋养层细胞区室到足月期的绒毛血管的时空转移表明纤连蛋白-5 在人胎盘发育中具有双重作用。
