Expression profiling of endogenous secretory receptor for advanced glycation end products in human organs

Expression profiling of endogenous secretory receptor for advanced glycation end products in human organs
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DOI:
10.1038/modpathol.3800450
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发表时间:
2005-10-01
期刊:
影响因子:
7.5
通讯作者:
Yamamoto, Y
Yamamoto, Y
中科院分区:
医学1区
文献类型:
--
作者:
Cheng, CM;Tsuneyama, K;Yamamoto, Y

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晚期糖基化终产物受体(receptor for advanced glycation end products,AGEs)是免疫球蛋白超家族的一种细胞表面多配体受体,参与神经元发育、糖尿病、炎症、神经退行性疾病和癌症等生理和病理过程。最近鉴定出一种新的内源性分泌诱饵形式(esophageal)的剪接变体,并认为其是修饰这些esophageal相关病症的有前景的候选者。在这里,我们用结构域特异性抗体研究了Esplatin和Esplatin蛋白的表达和分布。我们研究了各种各样的成年正常人的准备工作,从手术和尸检标本,使用组织芯片技术。结果显示,Escherichia coli广泛分布,我们将其表达分为四种模式。在模式A中,细胞质在神经元、血管内皮、肺细胞、间皮细胞、胰腺β细胞和巨噬细胞/单核细胞中弥漫染色。在模式B中,点状颗粒在面向胆管、唾液腺、消化道、肾小管、前列腺、皮肤、甲状腺和细支气管的腔表面的核上区域中染色.模式C表现为动脉壁间质区弥漫性染色。模式D显示分泌物质如甲状腺胶体、肾小管腔中的晶体和前列腺中的腺腔的弥漫性和强染色。这项研究提供了,第一次,一个组织病理学的基础,了解在人类中的生理作用,并将有助于阐明参与的病理过程中,埃斯帕酮和探索新的诊断和治疗概念。
The receptor for advanced glycation end products ( RAGE) is a cell surface multiligand receptor of the immunoglobulin superfamily, which participates in physiological and pathological processes such as neuronal development, diabetes, inflammation, neurodegenerative disorders, and cancer. A novel splice variant of RAGE- endogenous secretory decoy form ( esRAGE) was recently identified and is thought to be a prospective candidate to modify these RAGE- associated conditions. Here, we investigated the expression and distribution of esRAGE and RAGE proteins with domain- specific antibodies. We studied a wide variety of adult normal human preparations obtained from surgical and autopsy specimens using a tissue microarray technique. The results revealed that esRAGE was widely distributed and we classified its expression into four patterns. In pattern A, the cytoplasm is stained diffusely in neurons, vascular endothelium, pneumocytes, mesothelium, pancreatic beta cells, and macrophages/ monocytes. In pattern B, dot- like granules are stained in the supranuclear regions facing the luminal surface of the bile ducts, salivary glands, digestive tracts, renal tubules, prostate, skin, thyroid, and bronchioles. Pattern C is represented by diffuse staining in the stromal area of the arterial walls. Pattern D shows diffuse and strong staining of secreted materials such as thyroidal colloid, crystals in renal tubular lumen, and glandular lumen in prostate. This study provides, for the first time, a histopathological basis for understanding the physiological roles of esRAGE in humans, and will contribute to elucidating the participation of esRAGE in pathological processes and to exploring novel diagnostic and therapeutic concepts.