Dataset Information

MiR-146b-5p regulates bone marrow mesenchymal stem cell differentiation by SIAH2/PPARγ in aplastic anemia children and benzene-induced aplastic anemia mouse model.

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.

SUBMITTER: Li H

PROVIDER: S-EPMC7553565 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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miR-146b-5p regulates bone marrow mesenchymal stem cell differentiation by SIAH2/PPARγ in aplastic anemia children and benzene-induced aplastic anemia mouse model.

Li Huanhuan H Xu Xueju X Wang Dao D Zeng Li L Li Bai B Zhang Yuan Y Su Shufang S Wei Linlin L You Hongliang H Fang Yingqi Y Wang Yingchao Y Liu Yufeng Y

Cell cycle (Georgetown, Tex.) 20200825 19

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 di ...[more]

PMID: 32840137

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Project description:BackgroundPrevious studies have verified the dysfunction of mesenchymal stem cells (MSCs) for immunoregulation in acquired aplastic anemia (AA) patients. Exosomes derived from MSCs can partially substitute MSCs acting as immune regulator. Dysfunction of exosomes (Exos) derived from AA-MSC (AA-Exos) may play a key role in immunologic dissonance.MethodIn this study, CD3 + T cells were collected and cocultured with AA-Exos and exosomes derived from HD-MSC (HD-Exos). The proliferation, differentiation and activation of CD3 + T cells were detected to compare the immunosuppressive effects between AA-Exos and HD-Exos. An immune-mediated murine model of AA was structured to compare the therapeutic effect of AA-Exos and HD-Exos. Furthermore, total RNA including miRNA from exosomes we purified and total RNA of CD3 + T cells were extracted for RNA-seq in order to construct the miRNA-mRNA network for interactions and functional analysis.ResultsAA-Exos had impaired inhibition effects on CD3 + T cells in terms of cell proliferation, activation and differentiation compared with exosomes from HD-Exos. HD-Exos showed a more effective rescue of AA mice compared to AA-Exos. Importantly, we found some differentially expressed miRNA involved in immune response, such as miR-199, miR-128 and miR-486. The Gene Ontology analysis of differentially expressed genes (DEGs) revealed involvement of various cellular processes, such as lymphocyte chemotaxis, lymphocyte migration and response to interferon-gamma. The Kyoto Encyclopedia of Genes and Genomes analysis illustrated upregulation of critical pathways associated with T cell function after coculturing with AA-Exos compared with HD-Exos, such as graft-versus-host disease, Th17 cell differentiation and JAK-STAT signaling pathway. A miRNA-mRNA network was established to visualize the interaction between them.ConclusionIn summary, AA-Exos had impaired immunosuppressive effect on T cells, less ability to rescue AA mice and differently expressed miRNA profile, which might partly account for the pathogenesis of AA as well as provide a new target of AA treatment.

Dataset Information

MiR-146b-5p regulates bone marrow mesenchymal stem cell differentiation by SIAH2/PPARγ in aplastic anemia children and benzene-induced aplastic anemia mouse model.

Publications

miR-146b-5p regulates bone marrow mesenchymal stem cell differentiation by SIAH2/PPARγ in aplastic anemia children and benzene-induced aplastic anemia mouse model.

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