GPNMB promotes proliferation of developing eosinophils

S. Hwang, J. Kang, B. K. Kim, Tae Gi Uhm, Hye Jeong Kim, Hyune-Hwan Lee, B. Binas, I. Chung
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引用次数: 2

Abstract

Glycoprotein non-metastatic melanoma protein B (GPNMB) is a type I transmembrane protein that is expressed in a wide variety of cell types, including haematopoietic lineages. We previously demonstrated that GPNMB is one of the most highly expressed genes at an early and intermediate stage of eosinophil development. We herein examined GPNMB expression and its possible functional effect using cord blood (CB) CD34+ haematopoietic stem cells differentiating toward eosinophils during a 24-day culture period. Western blot and confocal microscopy analyses showed that GPNMB reached its highest levels at day 12 with most GPNMB-positive cells also expressing major basic protein 1 (MBP1), an eosinophil granule protein. GPNMB declined thereafter, but was still present at an appreciable level at day 24, the time when CB eosinophils most abundantly expressed MBP1 and were thus considered fully differentiated. When the developing CB cells were cultured in the presence of a blocking anti-GPNMB antibody, cell proliferation was significantly reduced. In agreement, ectopic expression of GPNMB in heterologous cells resulted in a significant increase in cell proliferation, while small interfering RNA of GPNMB inhibited the GPNMB-mediated proliferation. Thus, GPNMB is expressed in a temporal manner during eosinophil development and delivers a proliferative signal upon activation.
GPNMB促进发育中的嗜酸性粒细胞增殖
糖蛋白非转移性黑色素瘤蛋白B (GPNMB)是一种I型跨膜蛋白,在多种细胞类型中表达,包括造血谱系。我们之前已经证明GPNMB是嗜酸性粒细胞发育早期和中期最高度表达的基因之一。在此,我们利用脐带血(CB) CD34+造血干细胞在24天的培养期间向嗜酸性粒细胞分化,研究了GPNMB的表达及其可能的功能影响。Western blot和共聚焦显微镜分析显示,GPNMB在第12天达到最高水平,大多数GPNMB阳性细胞也表达主要碱性蛋白1 (MBP1),一种嗜酸性粒细胞颗粒蛋白。GPNMB随后下降,但在第24天仍以可观的水平存在,这是CB嗜酸性粒细胞最丰富表达MBP1的时候,因此被认为是完全分化的。当发育中的CB细胞在阻断抗gpnmb抗体存在下培养时,细胞增殖明显降低。与此一致的是,GPNMB在异种细胞中的异位表达导致细胞增殖显著增加,而GPNMB的小干扰RNA抑制GPNMB介导的增殖。因此,GPNMB在嗜酸性粒细胞发育过程中以时间方式表达,并在激活时传递增殖信号。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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