Blockade of the interaction between BMP9 and endoglin on erythroid progenitors promotes erythropoiesis in mice,Genes to Cells

当前位置： X-MOL 学术 › Genes Cells › 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.)

Blockade of the interaction between BMP9 and endoglin on erythroid progenitors promotes erythropoiesis in mice
Genes to Cells ( IF 1.3 ) Pub Date : 2021-08-01 , DOI: 10.1111/gtc.12887
Ayami Yamaguchi ₁ , Ikuo Hirano ₂ , Shiho Narusawa ₂ , Kiyoshi Shimizu ₁ , Hiroyuki Ariyama ₁ , Kengo Yamawaki ₁ , Kenji Nagao ₁ , Masayuki Yamamoto _{3,

4} , Ritsuko Shimizu _{2,

4}

Affiliation

Bone morphogenetic protein-9 (BMP9), a member of the transforming growth factor β (TGFβ) superfamily, plays important roles in the development and maintenance of various cell lineages via complexes of type I and type II TGFβ receptors. Endoglin is a coreceptor for several TGFβ family members, including BMP9, which is highly expressed in a particular stage of differentiation in erythroid cells as well as in endothelial cells. Although the importance of the interaction between BMP9 and endoglin for endothelial development has been reported, the contribution of BMP9 to endoglin-expressing erythroid cells remains to be clarified. To address this point, we prepared an anti-BMP9 antibody that blocks the BMP9-endoglin interaction. Of note, challenge with the antibody promotes erythropoiesis in wild-type mice but not in a mouse model of renal anemia in which erythropoietin (EPO) production in the kidneys is genetically ablated. While endoglin-positive erythroid progenitors are mainly maintained as progenitors when bone marrow-derived lineage-negative and cKit-positive cells are cultured in the presence of EPO and stem cell factor, the erythroid-biased accumulation of progenitors is impeded by the presence of BMP9. Our findings uncover an unrecognized role for BMP9 in attenuating erythroid differentiation via its interaction with endoglin on erythroid progenitors.

中文翻译：

阻断 BMP9 和内皮糖蛋白对红系祖细胞的相互作用促进小鼠红细胞生成

骨形态发生蛋白 9 (BMP9) 是转化生长因子 β (TGFβ) 超家族的成员，通过 I 型和 II 型 TGFβ 受体复合物在各种细胞谱系的发育和维持中发挥重要作用。Endoglin 是几个 TGFβ 家族成员的辅助受体，包括 BMP9，它在红细胞和内皮细胞的特定分化阶段高度表达。尽管已经报道了 BMP9 和内皮糖蛋白之间相互作用对内皮发育的重要性，但 BMP9 对表达内皮糖蛋白的红细胞的贡献仍有待阐明。为了解决这一点，我们制备了一种阻断 BMP9-内皮糖蛋白相互作用的抗 BMP9 抗体。值得注意的是，在野生型小鼠中，用抗体激发红细胞生成可促进红细胞生成，但在肾脏中的促红细胞生成素 (EPO) 产生被基因消除的肾性贫血小鼠模型中则不然。当在 EPO 和干细胞因子存在的情况下培养骨髓来源的谱系阴性和 cKit 阳性细胞时，内皮糖蛋白阳性红系祖细胞主要维持为祖细胞，而 BMP9 的存在阻碍了祖细胞偏红系的积累. 我们的研究结果揭示了 BMP9 通过其与红细胞祖细胞上的内皮糖蛋白相互作用来减弱红细胞分化中的未被认识的作用。当在 EPO 和干细胞因子存在的情况下培养骨髓来源的谱系阴性和 cKit 阳性细胞时，内皮糖蛋白阳性红系祖细胞主要维持为祖细胞，而 BMP9 的存在阻碍了祖细胞偏红系的积累. 我们的研究结果揭示了 BMP9 通过其与红细胞祖细胞上的内皮糖蛋白相互作用来减弱红细胞分化中的未被认识的作用。当在 EPO 和干细胞因子存在的情况下培养骨髓来源的谱系阴性和 cKit 阳性细胞时，内皮糖蛋白阳性红系祖细胞主要维持为祖细胞，而 BMP9 的存在阻碍了祖细胞偏红系的积累. 我们的研究结果揭示了 BMP9 通过其与红细胞祖细胞上的内皮糖蛋白相互作用来减弱红细胞分化中的未被认识的作用。

更新日期：2021-10-07

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