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人 NME1 在猪骨髓间充质干细胞神经分化中的潜在作用：NB-hNME1 作为人 NME1 抑制剂的应用。

The Potential Role of Human NME1 in Neuronal Differentiation of Porcine Mesenchymal Stem Cells: Application of NB-hNME1 as a Human NME1 Suppressor.

机构信息

Department of Biological Science, College of Natural Sciences, Wonkwang University, 460, Iksan-daero, Iksan-si 54538, Korea.

GreenBio Corp. Central Research, 201-19, Bubaljungand-ro, Bubal-eup, Icheon-si 17321, Korea.

出版信息

Int J Mol Sci. 2021 Nov 11;22(22):12194. doi: 10.3390/ijms222212194.

DOI:10.3390/ijms222212194
PMID:34830075
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8619003/
Abstract

This study aimed to investigate the effects of the human macrophage (MP) secretome in cellular xenograft rejection. The role of human nucleoside diphosphate kinase A (hNME1), from the secretome of MPs involved in the neuronal differentiation of miniature pig adipose tissue-derived mesenchymal stem cells (mp AD-MSCs), was evaluated by proteomic analysis. Herein, we first demonstrate that hNME1 strongly binds to porcine ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 (pST8SIA1), which is a ganglioside GD3 synthase. When hNME1 binds with pST8SIA1, it induces degradation of pST8SIA1 in mp AD-MSCs, thereby inhibiting the expression of ganglioside GD3 followed by decreased neuronal differentiation of mp AD-MSCs. Therefore, we produced nanobodies (NBs) named NB-hNME1 that bind to hNME1 specifically, and the inhibitory effect of NB-hNME1 was evaluated for blocking the binding between hNME1 and pST8SIA1. Consequently, NB-hNME1 effectively blocked the binding of hNME1 to pST8SIA1, thereby recovering the expression of ganglioside GD3 and neuronal differentiation of mp AD-MSCs. Our findings suggest that mp AD-MSCs could be a potential candidate for use as an additive, such as an immunosuppressant, in stem cell transplantation.

摘要

本研究旨在探讨人巨噬细胞（MP）分泌组在细胞异种移植排斥中的作用。通过蛋白质组学分析，评估了来自参与小型猪脂肪组织来源间充质干细胞（mp AD-MSCs）神经元分化的 MPs 分泌组中的人核苷酸二磷酸激酶 A（hNME1）的作用。在此，我们首次证明 hNME1 与猪 ST8 alpha-N-乙酰神经氨酸 alpha-2,8-唾液酸转移酶 1（pST8SIA1）强烈结合，后者是神经节苷脂 GD3 合酶。当 hNME1 与 pST8SIA1 结合时，它会诱导 mp AD-MSCs 中 pST8SIA1 的降解，从而抑制神经节苷脂 GD3 的表达，随后抑制 mp AD-MSCs 的神经元分化。因此，我们产生了特异性结合 hNME1 的纳米抗体（NB），命名为 NB-hNME1，并评估了 NB-hNME1 阻断 hNME1 与 pST8SIA1 结合的抑制作用。结果，NB-hNME1 有效地阻断了 hNME1 与 pST8SIA1 的结合，从而恢复了神经节苷脂 GD3 的表达和 mp AD-MSCs 的神经元分化。我们的研究结果表明，mp AD-MSCs 可能是作为干细胞移植中免疫抑制剂等添加剂的潜在候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7ae/8619003/5c1f28073202/ijms-22-12194-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7ae/8619003/5c1f28073202/ijms-22-12194-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7ae/8619003/5c1f28073202/ijms-22-12194-g003.jpg

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