Disease-specific extracellular matrix composition regulates placental trophoblast fusion efficiency,Biomaterials Science

当前位置： X-MOL 学术 › Biomater. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Disease-specific extracellular matrix composition regulates placental trophoblast fusion efficiency
Biomaterials Science ( IF 5.8 ) Pub Date : 2021-09-27 , DOI: 10.1039/d1bm00799h
Prabu Karthick Parameshwar ₁ , Lucas Sagrillo-Fagundes _{2,

3} , Caroline Fournier ₃ , Sylvie Girard ₄ , Cathy Vaillancourt _{3,

4} , Christopher Moraes _{1,

2,

5,

6}

Affiliation

The placental syncytiotrophoblast is a multinucleated layer that regulates transport between the mother and fetus. Fusion of trophoblasts is essential to form this layer, but this process can be disrupted in pregnancy-related disorders such as preeclampsia. Disease progression is also associated with changes in the extracellular matrix (ECM), but whether disease-specific ECM compositions play any causal role in establishing syncytiotrophoblast disease phenotypes remains unknown. Here, we develop a decellularization-based platform to isolate and characterize the role of human placental ECM composition on cell function, while controlling for the confounding effects of matrix structure and mechanics that can arise in conventional tissue decellularization/recellularization experiments. Using this approach, we demonstrate that ECM compositional changes that occur in preeclampsia have a statistically significant effect on adhesion, spreading, and fusion of placental trophoblasts. Proteomic analysis of ECM content then allowed us to identify and recreate selected differences in matrix composition; indicating that replacement of normally present Type IV Collagen by Type I Collagen in preeclampsia significantly affects fusion efficiency. These results indicate that disease-specific matrix compositions can play an important role in trophoblast fusion, suggesting novel matrix-targeting therapeutic strategies for pregnancy-related disorders. More broadly, this work demonstrates the utility of a decellularization-based approach in understanding the functional contributions of matrix composition in driving cellular disease phenotypes.

中文翻译：

疾病特异性细胞外基质成分调节胎盘滋养层融合效率

胎盘合体滋养层是一个多核层，可调节母亲和胎儿之间的运输。滋养层的融合对于形成这一层至关重要，但这一过程可能会在与妊娠相关的疾病（如先兆子痫）中被破坏。疾病进展也与细胞外基质 (ECM) 的变化有关，但疾病特异性 ECM 成分是否在建立合体滋养细胞疾病表型中发挥任何因果作用仍然未知。在这里，我们开发了一个基于去细胞化的平台，以分离和表征人类胎盘 ECM 成分对细胞功能的作用，同时控制在传统组织去细胞化/再细胞化实验中可能出现的基质结构和力学的混杂影响。使用这种方法，我们证明先兆子痫中发生的 ECM 成分变化对胎盘滋养细胞的粘附、扩散和融合具有统计学意义。ECM 内容的蛋白质组学分析使我们能够识别和重建基质组成中的选定差异；表明在先兆子痫中用 I 型胶原替代正常存在的 IV 型胶原显着影响融合效率。这些结果表明疾病特异性基质组合物可以在滋养层融合中发挥重要作用，这表明了针对妊娠相关疾病的新型基质靶向治疗策略。更广泛地说，这项工作证明了基于去细胞化的方法在理解基质组成在驱动细胞疾病表型中的功能贡献方面的效用。

更新日期：2021-10-06

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11