PDF(Pubmed)
Abstract：
We recently showed that 6-sulfo sialyl N-acetyllactosamine (LacNAc) in O-linked glycans recognized by the CL40 antibody is abundant in the pleural mesothelium under physiological conditions and that these glycans undergo complementary synthesis by GlcNAc6ST2 (encoded by Chst4) and GlcNAc6ST3 (encoded by Chst5) in mice. GlcNAc6ST3 is essential for the synthesis of R-10G-positive keratan sulfate (KS) in the brain. The predicted minimum epitope of the R-10G antibody is a dimeric asialo 6-sulfo LacNAc. Whether R-10G-reactive KS/sulfated LacNAc oligosaccharides are also present in the pleural mesothelium was unknown. The question of which GlcNAc6STs are responsible for R-10G-reactive glycans was an additional issue to be clarified. Here, we show that R-10G-reactive glycans are as abundant in the pulmonary pleura as CL40-reactive glycans and that GlcNAc6ST3 is only partially involved in the synthesis of these pleural R-10G glycans, unlike in the adult brain. Unexpectedly, GlcNAc6ST2 is essential for the synthesis of R-10G-positive KS/sulfated LacNAc oligosaccharides in the lung pleura. The type of GlcNAc6ST and the magnitude of its contribution to KS glycan synthesis varied among tissues in vivo. We show that GlcNAc6ST2 is required and sufficient for R-10G-reactive KS synthesis in the lung pleura. Interestingly, R-10G immunoreactivity in KSGal6ST (encoded by Chst1) and C6ST1 (encoded by Chst3) double-deficient mouse lungs was markedly increased. MUC16, a mucin molecule, was shown to be a candidate carrier protein for pleural R-10G-reactive glycans. These results suggest that R-10G-reactive KS/sulfated LacNAc oligosaccharides may play a role in mesothelial cell proliferation and differentiation. Further elucidation of the functions of sulfated glycans synthesized by GlcNAc6ST2 and GlcNAc6ST3, such as R-10G and CL40 glycans, in pathological conditions may lead to a better understanding of the underlying mechanisms of the physiopathology of the lung mesothelium.
摘要：
我们最近表明，在生理条件下，CL40抗体识别的O连接聚糖中的6-磺基唾液酸N-乙酰乳糖胺（LacNAc）在胸膜间皮中含量丰富，并且这些聚糖通过GlcNAc6ST2（由Chst4编码）和GlcNAc6ST3（由Chst5编码）在小鼠中进行互补合成。GlcNAc6ST3对于大脑中R-10G阳性硫酸角质素（KS）的合成至关重要。R-10G抗体的预测最小表位是二聚体唾液酸6-磺基LacNAc。胸膜间皮中是否也存在R-10G反应性KS/硫酸化LacNAc寡糖尚不清楚。哪个GlcNAc6ST负责R-10G反应性聚糖的问题是需要澄清的另一个问题。这里,我们显示R-10G反应性聚糖在肺胸膜中与CL40反应性聚糖一样丰富，并且GlcNAc6ST3仅部分参与这些胸膜R-10G聚糖的合成，与成年人的大脑不同。出乎意料的是,GlcNAc6ST2对于在肺胸膜中合成R-10G阳性KS/硫酸化LacNAc寡糖是必需的。GlcNAc6ST的类型及其对KS聚糖合成的贡献大小在体内组织之间变化。我们表明，GlcNAc6ST2是肺胸膜中R-10G反应性KS合成所必需且足够的。有趣的是,KSGal6ST（由Chst1编码）和C6ST1（由Chst3编码）双缺陷小鼠肺中的R-10G免疫反应性明显增加。MUC16，一种粘蛋白分子，被证明是胸膜R-10G反应性聚糖的候选载体蛋白。这些结果表明，R-10G反应性KS/硫酸化LacNAc寡糖可能在间皮细胞增殖和分化中起作用。进一步阐明由GlcNAc6ST2和GlcNAc6ST3合成的硫酸化聚糖的功能，例如R-10G和CL40聚糖，在病理条件下，可能会导致更好地了解肺间皮病理生理学的潜在机制。
