EXPRESSION AND DISTRIBUTION OF OSTEOPONTIN IN HUMAN TISSUES - WIDESPREAD ASSOCIATION WITH LUMINAL EPITHELIAL SURFACES

EXPRESSION AND DISTRIBUTION OF OSTEOPONTIN IN HUMAN TISSUES - WIDESPREAD ASSOCIATION WITH LUMINAL EPITHELIAL SURFACES
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DOI:
10.1091/mbc.3.10.1169
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发表时间:
1992-10-01
影响因子:
3.3
通讯作者:
SENGER, DR
SENGER, DR
中科院分区:
生物学3区
文献类型:
--
作者:
BROWN, LF;BERSE, B;SENGER, DR

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骨桥蛋白是一种具有甘氨酸-精氨酸-甘氨酸-天冬氨酸-丝氨酸(GRGDS)细胞结合结构域的糖蛋白,已在骨骼中描述,并且已知在其他器官(特别是肾脏)中表达。本研究的目的是通过免疫组化、原位杂交和北方分析等多方面的方法,确定骨桥蛋白在各种正常成人组织中的合成和沉积分布。免疫组织化学研究揭示了一个意想不到的发现,即骨桥蛋白沉积在胃肠道、胆囊、胰腺、泌尿道和生殖道、肺、乳腺、唾液腺和汗腺的上皮细胞的特定群体的腔表面上作为突出层。北方分析表明胆囊是骨桥蛋白基因转录的主要位点,其转录量与肾脏相当,免疫印迹法在胆汁中鉴定出骨桥蛋白。原位杂交定位骨桥蛋白基因转录本主要定位于各种器官的上皮细胞以及肠壁的神经节细胞。上皮细胞来源的骨桥蛋白,如骨源性骨桥蛋白,促进GRGDS依赖的细胞扩散的附着试验。我们推测上皮细胞分泌的骨桥蛋白结合管腔表面的整合素。总的来说,这些发现表明骨桥蛋白在许多与外部环境沟通的腔上皮表面上发挥重要作用。
Osteopontin, a glycoprotein with a glycine-arginine-glycine-aspartate-serine (GRGDS) cell-binding domain, has been described in bone and is also known to be expressed in other organs, particularly kidney. The goal of the present work was to define the distribution osteopontin synthesis and deposition in a wide variety of normal adult human tissues using a multifaceted approach that included immunohistochemistry, in situ hybridization, and Northern analysis. Immunohistochemical studies have revealed the unexpected finding that osteopontin is deposited as a prominent layer at the luminal surfaces of specific populations of epithelial cells of the gastrointestinal tract, gall bladder, pancreas, urinary and reproductive tracts, lung, breast, salivary glands, and sweat glands. Northern analyses identified gallbladder as a major site of osteopontin gene transcription comparable in magnitude with that of kidney, and immunoblotting identified osteopontin in bile. In situ hybridization localized osteopontin gene transcripts predominantly to the epithelium of a variety of organs as well as to ganglion cells of bowel wall. Osteopontin of epithelial cell origin, like bone-derived osteopontin, promoted GRGDS-dependent cell spreading in attachment assays. We postulate that osteopontin secreted by epithelium binds integrins on luminal surfaces. Collectively, these findings suggest an important role for osteopontin on many luminal epithelial surfaces communicating with the external environment.