LIGHT (TNFSF14) Increases the Survival and Proliferation of Human Bone Marrow-Derived Mesenchymal Stem Cells.
LIGHT (TNFSF14) Increases the Survival and Proliferation of Human Bone Marrow-Derived Mesenchymal Stem Cells.
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DOI：
10.1371/journal.pone.0166589
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Kim H
中科院分区：
文献类型：
--
作者：
Heo SK;Noh EK;Gwon GD;Kim JY;Jo JC;Choi Y;Koh S;Baek JH;Min YJ;Kim H
LIGHT （hveml, TNFSF14，或CD258）是淋巴毒素的同源实体，具有诱导性质，能够与单纯疱疹病毒糖蛋白D竞争疱疹病毒进入介质(HVEM)/肿瘤坏死因子（TNF）相关2，是TNF超家族的成员。它以三聚体形式在活化的T细胞和树突状细胞（dc）上表达，有三种受体：HVEM、LT-β受体（LTβR）和诱饵受体3 （DcR3）。到目前为止，已知有三种具有不同细胞表达模式的受体与LIGHT相互作用。滤泡dc和基质细胞通过LTβR结合LIGHT。我们监测了LIGHT对人骨髓间充质干细胞（BM-MSCs）的影响。首先，我们检查了BM-MSCs的阴性和阳性分化标志物。我们通过对细胞进行脂肪形成（油红O染色）、软骨形成（阿利新蓝染色）和成骨形成（茜素红染色）的染色来证实MSCs的质量。rhLIGHT处理后，我们监测细胞的计数、活力、增殖和细胞周期分布。ELISA法检测rhLIGHT对PDGF和TGFβ的产生，免疫印迹法研究rhLIGHT作用的生物学机制。LTβR在人BM-MSCs表面组成性表达。rhLIGHT处理后细胞数量和活力增加。S/G2/M期增加诱导BM-MSC增殖。rhLIGHT处理后，不仅cyclin B1、D1、D3、E等多种细胞周期蛋白的表达增加，而且CDK1、CDK2的表达增加，而p27的表达减少。由STAT3和Smad3激活介导的rhlight诱导的PDGF和TGFβ的产生加速了BM-MSC的增殖。因此，LIGHT和LTβR相互作用增加了人BM-MSCs的存活和增殖，因此，LIGHT可能在干细胞治疗中发挥重要作用。
LIGHT (HVEM-L, TNFSF14, or CD258), an entity homologous to lymphotoxins, with inducible nature and the ability to compete with herpes simplex virus glycoprotein D for herpes virus entry mediator (HVEM)/tumor necrosis factor (TNF)-related 2, is a member of the TNF superfamily. It is expressed as a homotrimer on activated T cells and dendritic cells (DCs), and has three receptors: HVEM, LT-β receptor (LTβR), and decoy receptor 3 (DcR3). So far, three receptors with distinct cellular expression patterns are known to interact with LIGHT. Follicular DCs and stromal cells bind LIGHT through LTβR. We monitored the effects of LIGHT on human bone marrow-derived mesenchymal stem cells (BM-MSCs). At first, we checked the negative and positive differentiation markers of BM-MSCs. And we confirmed the quality of MSCs by staining cells undergoing adipogenesis (Oil Red O staining), chondrogenesis (Alcian blue staining), and osteogenesis (Alizarin red staining). After rhLIGHT treatment, we monitored the count, viability, and proliferation of cells and cell cycle distribution. PDGF and TGFβ production by rhLIGHT was examined by ELISA, and the underlying biological mechanisms were studied by immunoblotting by rhLIGHT treatment. LTβR was constitutively expressed on the surface of human BM-MSCs. Cell number and viability increased after rhLIGHT treatment. BM-MSC proliferation was induced by an increase in the S/G2/M phase. The expression of not only diverse cyclins such as cyclin B1, D1, D3, and E, but also CDK1 and CDK2, increased, while that of p27 decreased, after rhLIGHT treatment. RhLIGHT-induced PDGF and TGFβ production mediated by STAT3 and Smad3 activation accelerated BM-MSC proliferation. Thus, LIGHT and LTβR interaction increases the survival and proliferation of human BM-MSCs, and therefore, LIGHT might play an important role in stem cell therapy.
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