Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
J Nutr Biochem. 2021 Jul;93:108626. doi: 10.1016/j.jnutbio.2021.108626. Epub 2021 Mar 8.
Protein malnutrition causes anemia and leukopenia as it reduces hematopoietic precursors and impairs the production of mediators that regulate hematopoiesis. Hematopoiesis occurs in distinct bone marrow niches that modulate the processes of differentiation, proliferation and self-renewal of hematopoietic stem cells (HSCs). Mesenchymal stem cells (MSCs) contribute to the biochemical composition of bone marrow niches by the secretion of several growth factors and cytokines, and they play an important role in the regulation of HSCs and hematopoietic progenitors. In this study, we investigated the effect of protein malnutrition on the hematopoietic regulatory function of MSCs. C57BL/6NTaq mice were divided into control and protein malnutrition groups, which received, respectively, a normal protein diet (12% casein) and a low protein diet (2% casein). The results showed that protein malnutrition altered the synthesis of SCF, TFG-β, Angpt-1, CXCL-12, and G-CSF by MSCs. Additionally, MSCs from the protein malnutrition group were not able to maintain the lymphoid, granulocytic and megakaryocytic-erythroid differentiation capacity compared to the MSCs of the control group. In this way, the comprehension of the role of MSCs on the regulation of the hematopoietic cells, in protein malnutrition states, is for the first time showed. Therefore, we infer that hematopoietic alterations caused by protein malnutrition are due to multifactorial alterations and, at least in part, the MSCs' contribution to hematological impairment.
蛋白质营养不良会导致贫血和白细胞减少症，因为它会减少造血前体细胞并损害调节造血的介质的产生。造血发生在不同的骨髓龛中，这些龛调节造血干细胞（HSCs）的分化、增殖和自我更新过程。间充质干细胞（MSCs）通过分泌几种生长因子和细胞因子为骨髓龛的生化组成做出贡献，并且在调节 HSCs 和造血祖细胞方面发挥重要作用。在这项研究中，我们研究了蛋白质营养不良对 MSCs 造血调节功能的影响。C57BL/6NTaq 小鼠分为对照组和蛋白质营养不良组，分别接受正常蛋白质饮食（12%酪蛋白）和低蛋白质饮食（2%酪蛋白）。结果表明，蛋白质营养不良改变了 MSCs 中 SCF、TGF-β、Angpt-1、CXCL-12 和 G-CSF 的合成。此外，与对照组的 MSCs 相比，蛋白质营养不良组的 MSCs 无法维持淋巴样、粒细胞样和巨核细胞-红细胞分化能力。通过这种方式，首次显示了 MSCs 在调节造血细胞方面的作用。因此，我们推断蛋白质营养不良引起的造血改变是由于多因素改变引起的，至少部分原因是 MSCs 对血液学损害的贡献。
