ABSTRACT

This study aimed to reveal the mechanism of miR-146b-5p in the differentiation of bone marrow mesenchymal stem cells (BMSCs) derived from children with aplastic anemia (AA). Here, we found that miR-146b-5p was highly expressed in BMSCs from children with AA, and the BMSCs surface markers expressions in BMSCs derived from children with AA and the healthy controls exerted no significant differences. Besides, the overexpression of miR-146b-5p in normal human-derived BMSCs promoted the adipogenic differentiation of BMSCs. Furthermore, miR-146b-5p negatively regulated SIAH2 luciferase activity, and the interference with miR-146b-5p reduced the stability of PPARγ protein and inhibited SIAH2-mediated ubiquitination of PPARγ protein. Besides, the interference with miR-146b-5p was beneficial for ameliorating AA in a mouse model of AA. Overall, our results found that miR-146b-5p was highly expressed in BMSCs from children with AA, and our further studies indicated that miR-146b-5p improved AA via promoting SIAH2-mediated ubiquitination of PPARγ protein.

摘要

本研究旨在揭示miR-146b-5p在再生障碍性贫血（AA）儿童骨髓间充质干细胞（BMSCs）分化中的作用机制。在这里，我们发现 miR-146b-5p 在 AA 儿童的 BMSC 中高表达，而 AA 儿童和健康对照组的 BMSC 表面标志物的表达没有显着差异。此外，miR-146b-5p在正常人源性骨髓间充质干细胞中的过表达促进了骨髓间充质干细胞的成脂分化。此外，miR-146b-5p 负向调节 SIAH2 荧光素酶活性，干扰 miR-146b-5p 降低 PPARγ 蛋白的稳定性并抑制 SIAH2 介导的 PPARγ 蛋白泛素化。此外，干扰 miR-146b-5p 有利于改善 AA 小鼠模型中的 AA。总体，