水通道蛋白在人喉组织的表达

目的:探讨水通道在喉组织中的分布及可能的功能。方法:通过RT-PCR、免疫印迹分别在RNA和蛋白水平明确喉组织中水通道的种类;采用免疫组织化学法对喉组织中的水通道蛋白进行定位分析。结果:水通道AQP1和AQP3在喉组织中表达:水通道蛋白AQP1在喉室黏膜假复层纤毛柱状上皮的纤毛、黏膜固有层的血管内皮及喉部神经纤维和神经节中表达;AQP3在喉黏膜鳞状上皮和固有层腺体上有表达。结论:喉组织中的水通道蛋白AQP1和AQP3在维持喉正常生理功能特别是发声中可能具有重要的作用。     

水通道蛋白1与肿瘤

<正>水通道蛋白家族是位于生物膜上具有快速水转运及离子转运功能的一族蛋白质。水通道蛋白1(Aquapor-in-1,AQP1)是第一个被发现的水通道蛋白,研究发现其不仅能介导水及离子转运,还对细胞内外气体交换、肿瘤血管的生成及细胞迁移产生重要影响     

肿瘤治疗的新途径-抗肿瘤血管生成的生化和基因治疗

新生血管对于肿瘤的生长、浸润和转移有重要意义.体积超过1mm3～2mm3的肿瘤不仅需要新生血管维持营养供给和排泄代谢产物,还需要提供有利于转移的通道.新生血管形成包括内皮细胞的激活、增殖、迁移、血管基底膜的破坏、血管和血管网的形成,以及先前存在的血管网的连接等过程.抑制新生血管的生成可使肿瘤细胞进入休眠状态并诱导其凋亡.目前用抗血管生成来达到对肿瘤的治疗目的已不再是理论上的可能,而是一个渐趋成熟、实用的治疗方法.我们仅就此作一简要介绍.     

聚集蛋白和CD34在良性与恶性肝脏病变鉴别诊断中的作用

聚集蛋白是硫酸类肝素蛋白聚糖家族中的一个成员,因其正常情况下表达于肝脏胆管和血管基膜,而被认为是胆管和血管的标记物.正常肝组织中很少表达聚集蛋白,肝硬化中因胆小管反应性增生和纤维间隔新的血管形成而表达增加,肝细胞癌中肿瘤新生血管形成聚集蛋白也表达增加,提示聚集蛋白可能作为肝细胞癌诊断的一种标记物.     

一个肿瘤区新生血管内皮细胞的标志物

以肝癌细胞培养上清诱导增生的人脐静脉内皮细胞作为抗原，免疫Ｂａｌｂ／ｃ小鼠，获得１株单克隆抗体（ｍＡｂ）ＢＶＥ－１。该ｍＡｂ具有与肿瘤区增生血管内皮细胞结合而不与正常组织血管内皮细胞结合的特点，其相应抗原的相对分子质量（Ｍｒ）为１５００００，为一种含唾液酸的糖脂蛋白。ｍＡｂＢＶＥ－１与内皮细胞结合后可抑制其生长、移动和血管样结构形成。这一抗原可能是血管新生时表达的一种特异性标志物，其抗体可望成为靶向肿瘤区血管的药物载体。     

ATP敏感性钾通道蛋白在缓激肽选择性开放血肿瘤屏障中的表达

目的 探讨ATP敏感性钾通道蛋白在缓激肽选择性开放血肿瘤屏障中的作用.方法 建立大鼠脑胶质瘤模型, 颈内动脉灌注缓激肽后,采用免疫组化SABC法和 Western blot法测定肿瘤组织ATP敏感性钾通道蛋白的功能亚基Kir6.2的分布和表达的变化.结果 脑胶质瘤大鼠经颈内动脉灌注缓激肽后,其肿瘤内血管内皮细胞的 Kir6.2蛋白表达比对照组显著增多, 且以灌注后10 min 增加最为显著. 结论 ATP敏感性钾通道蛋白表达上调可能是缓激肽选择性开放血肿瘤屏障的重要机制之一.     

水通道蛋白1和3在腰椎间盘退变组织中的表达

背景：腰椎间盘退变由多种因素引起,水通道蛋白变化规律在腰椎间盘退变中的作用研究较少。 目的：比较正常腰椎间盘组织及退变腰椎间盘组织中水通道蛋白1、水通道蛋白3的表达。 方法：收集大理学院附属医院骨科手术切除腰椎爆裂骨折患者腰椎间盘组织15份,退变椎间盘组织15 份,应用苏木精-伊红染色、免疫组织化学染色方法观察水通道蛋白1、水通道蛋白3的表达,测量平均吸光度值。 结果与结论：苏木精-伊红染色结果显示对照组椎间盘组织结构清晰,胶原纤维走形清楚,组织轻微水肿无黏液样变,病例组组织结构模糊紊乱,胶原纤维增生粗大、走行紊乱,组织炎性水肿严重、坏死黏液样变。免疫组织化学方法显示病例组水通道蛋白1、水通道蛋白3平均吸光度值明显低于对照组(P < 0.01),提示水通道蛋白1、水通道蛋白3减少可能是腰椎间盘退变因素之一。     

水通道蛋白1与内皮细胞功能

 水通道蛋白1（AQP1）是目前唯一发现在内皮有表达的水通道蛋白,在肾脏尿浓缩机制、小肠吸收乳糜微粒和角膜内皮的液体平衡中有重要作用;在血管内皮细胞中促进NO和CO2转运,调节血管舒缩功能,与心肌缺血后水肿和坏死关系密切,促进内皮细胞迁移,影响血管形成和肿瘤播散。     

血管生成抑制因子与肿瘤转移的抑制

新生血管形成是肿瘤生长和转移的重要环节，是肿瘤细胞进入血液的主要通道，受到血管生成刺激因子和抑制因子（ 如ａｎｇｉｏｓｔａｔｉｎ 和ｅｎｄｏｓｔａｔｉｎ） 等物质的调节。血管生成抑制因子通过抑制内皮细胞的生成和迁移而显示出强烈的抗肿瘤作用，其毒性低、不易产生耐药性，具有广泛的应用前景     

脑水通道蛋白的分布、功能及调控机制

背景：在哺乳动物脑中主要表达的水通道蛋白是水通道蛋白1、水通道蛋白4和水通道蛋白9,其他的仅为零星表达。目前国内外尚未见到系统分析维持脑正常生理功能的水通道蛋白分布、功能及其调节机制的综述报道。 目的：综述近年国内外维持脑正常生理功能的水通道蛋白分布、功能及其调节机制的研究进展。 方法：应用计算机检索1980年1月至2013年7月PubMed数据库、中国期刊全文数据库有关脑正常生理功能维持中水通道蛋白分布、功能及其调节机制的文章,英文检索词“AQP1, AQP4,AQP9, function, brain, adjusting mechanism”;中文检索词“水通道蛋白,功能,脑,调节机制”。共检索到163篇相关文献,85篇文献符合纳入标准。 结果与结论：近年来,有大量学者对脑水通道蛋白的表达、功能及其调节机制进行了较深层次的研究,具体归纳为如下3个方面：①水通道蛋白1主要表达于脑室脉络丛参与脑脊液的形成;在其他类型的细胞中,气体小分子CO2,NO,NH3 及O2也可通过水通道蛋白1。②水通道蛋白4主要表达在胶质细胞足突、胶质界膜以及室管膜中,帮助水进出脑组织,并加速胶质细胞迁移及改变神经活动。③水通道蛋白9主要分布于星形胶质细胞及儿茶酚胺等神经元中,主要功能是参与脑内能量代谢。水通道蛋白被认为是对脑中水运输提供关键路径的主要水通道,有关水通道蛋白分布、功能及调控机制的研究对于攻克脑相关疾病起重要作用。水通道蛋白在维持脑正常生理及相关疾病中表达的调节机制尚未明晰,相关分子信号通路尚待更加深入、系统地研究。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

Aquaporins—new players in cancer biology

The aquaporins (AQPs) are small, integral-membrane proteins that selectively transport water across cell plasma membranes. A subset of AQPs, the aquaglyceroporins, also transport glycerol. AQPs are strongly expressed in tumor cells of different origins, particularly aggressive tumors. Recent discoveries of AQP involvement in cell migration and proliferation suggest that AQPs play key roles in tumor biology. AQP1 is ubiquitously expressed in tumor vascular endothelium, and AQP1-null mice show defective tumor angiogenesis resulting from impaired endothelial cell migration. AQP-expressing cancer cells show enhanced migration in vitro and greater local tumor invasion, tumor cell extravasation, and metastases in vivo. AQP-dependent cell migration may involve AQP-facilitated water influx into lamellipodia at the front edge of migrating cells. The aquaglyceroporin AQP3, which is found in normal epidermis and becomes upregulated in basal cell carcinoma, facilitates cell proliferation in different cell types. Remarkably, AQP3-null mice are resistant to skin tumorigenesis by a mechanism that may involve reduced tumor cell glycerol metabolism and ATP generation. Together, the data suggest that AQP expression in tumor cells and tumor vessels facilitates tumor growth and spread, suggesting AQP inhibition as a novel antitumor therapy.     

Aquaporins and cell migration

Aquaporin (AQP) water channels are expressed primarily in cell plasma membranes. In this paper, we review recent evidence that AQPs facilitate cell migration. AQP-dependent cell migration has been found in a variety of cell types in vitro and in mice in vivo. AQP1 deletion reduces endothelial cell migration, limiting tumor angiogenesis and growth. AQP4 deletion slows the migration of reactive astrocytes, impairing glial scarring after brain stab injury. AQP1-expressing tumor cells have enhanced metastatic potential and local infiltration. Impaired cell migration has also been seen in AQP1-deficient proximal tubule epithelial cells, and AQP3-deficient corneal epithelial cells, enterocytes, and skin keratinocytes. The mechanisms by which AQPs enhance cell migration are under investigation. We propose that, as a consequence of actin polymerization/depolymerization and transmembrane ionic fluxes, the cytoplasm adjacent to the leading edge of migrating cells undergoes rapid changes in osmolality. AQPs could thus facilitate osmotic water flow across the plasma membrane in cell protrusions that form during migration. AQP-dependent cell migration has potentially broad implications in angiogenesis, tumor metastasis, wound healing, glial scarring, and other events requiring rapid, directed cell movement. AQP inhibitors may thus have therapeutic potential in modulating these events, such as slowing tumor growth and spread, and reducing glial scarring after injury to allow neuronal regeneration.     

水通道蛋白与肿瘤

水通道蛋白（AQPs）是一类小分子质量的、膜内嵌蛋白,它所介导的自由水快速被动的跨生物膜转运,是水进出细胞的主要途径。AQPs大量表达于不同组织来源的肿瘤细胞,特别是侵袭性肿瘤。AQPs高表达的肿瘤细胞在体外表现为较强的迁移能力,体内则表现为局部侵袭力增强,渗出增多以及转移灶增多。抑制AQPs的表达将有可能为肿瘤的治疗提供帮助。     

Aquaporin-1 in breast cancer

The canonical function of aquaporin (AQP) water channels is to facilitate passive transport of water across cellular membranes making them essential in the regulation of body water homeostasis. Moreover, AQPs, including AQP1, have been found to be overexpressed in multiple cancer types, including breast cancer, where AQP1 overexpression is associated with poor prognosis. AQPs have been shown to affect cellular processes associated with cancer progression and spread including cell migration, angiogenesis, and proliferation. Moreover, AQPs can regulate levels of adhesion proteins at cell–cell junctions, a regulatory role, which is still largely unexplored in cancer. Understanding the molecular mechanisms of how AQP1 contributes to breast cancer progression and metastatic processes is essential to establish AQP1 as a biomarker and to develop targeted anticancer treatments for breast cancer patients. This mini-review focuses on the role of AQP1 in breast cancer.     

肺脏的水孔蛋白家族

90年代以来 ,作为膜上水分子通道的水孔蛋白(ａｑｕａｐｏｒｉｎｓ ,ＡＱＰｓ)家族克隆成功[1,2 ] ,对自由水被动跨膜转运机制做出更加形象而深入的解释。肺脏的许多生理功能都有水分子运动的参与 ,同时许多肺脏疾病 ,如哮喘、肺水肿和急性呼吸窘迫综合征等也涉及肺内水运动平衡的紊乱。因此肺内水孔蛋白的分布及其病理生理意义日益受到重视。1　水孔蛋白的结构与功能特点水孔蛋白属于膜主体内在蛋白 (ｍａｊｏｒｉｎｔｅｒｎａｌｐｒｏｔｅｉｎ ,ＭＩＰ)家族的成员 ,目前在人类和哺乳动物身上共发现 10个亚型 ,广泛分布于多个组织器官 ,具…     

Intracellular aquaporins: clues for intracellular water transport?

Aquaporins (AQPs) are usually present at the plasma membrane to regulate influx and outflow of water and small molecules. They are important for the regulation of water homeostasis for the cells and organisms. AQPs are also present inside the cell, at the membranes of intracellular organelles. The roles of such AQPs have not yet been established. They will be clues to clarify the mechanisms of water and small solutes movements inside the cell. Recently, a new AQP subfamily has been identified with highly deviated asparagine-proline-alanine boxes, signature sequences for AQP. With limited homology less than 20%, this subfamily will be a superfamily of AQPs. Accordingly, it was tentatively named "superaquaporin subfamily," which is so far only present in multicellular organisms including plants, insects, nematodes, and vertebrates. Some superaquaporins are functionally water channels and localized intracellularly. AQP11, one of the two superaquaporins in mammals, has been shown to be important for the development of the proximal tubule as its disruption produced neonatally fatal polycystic kidneys in mice. Hence, recent identification of intracellular AQPs will open new areas of research on cell biology and expand the scope of AQPs.     

胎儿发育中水通道蛋白的免疫组化观察

目的观察胎儿器官和组织发育过程中水通道蛋白(AQPs)的表达特征,初步探讨AQPs对胎儿发育进程的生物意义。方法14～38周胎儿共12例,取用肾脏、肺脏、唾液腺、甲状腺和胃等器官,常规固定、石蜡包埋和切片;用免疫组化S-P法,检测AQPs(AQP1、AQP2和AQP4)在胎儿不同胎龄器官组织中的表达。结果胎儿肾脏中AQPs定位于近端小管和集合管系统;胎肺中AQPs的表达随肺泡发育分化而迁移,始终定位于肺泡上皮;晚期胎肺中AQPs于肺泡及呼吸道上皮均有表达;胎16周起检出AQPs反应于唾液腺、胃腺和胰腺等消化腺,同时甲状腺中AQPs在滤泡上皮也有活跃表达。结论胎肾中AQPs的表达与肾的重吸收功能直接相关;胎肺内AQPs的表达反映肺泡上皮分化的轨迹,其调节水分的作用为肺泡发育提供空间;AQPs介导细胞内外水分的转运不但调节消化腺的分泌还参与调节甲状腺滤泡的激素合成和分泌过程。表明AQPs在胎儿发育过程,对各器官中水转运功能的成熟起重要作用。     

High-grade ovarian cancer secreting effective exosomes in tumor angiogenesis

Ovarian cancer, the most lethal gynecological cancer, related closely to tumor stage. High-grade ovarian cancer always results in a late diagnose and high recurrence, which reduce survival within five years. Until recently, curable therapy is still under research and anti-angiogenesis proves a promising way. Tumor-derived exosomes are essential in tumor migration and metastases such as angiogenesis is enhanced by exosomes. In our study, we have made comparison between high-grade and unlikely high-grade serous ovarian cancer cells on exosomal function of endothelial cells proliferation, migration and tube formation. Exosomes derived from high-grade ovarian cancer have a profound impact on angiogenesis with comparison to unlikely high-grade ovarian cancer. Proteomic profiles revealed some potential proteins involved in exosomal function of angiogenesis such as ATF2, MTA1, ROCK1/2 and so on. Therefore, exosomes plays an influential role in angiogenesis in ovarian serous cancer and also function more effectively in high-grade ovarian cancer cells.     

Aquaporin‐1 expression in the chick embryo chorioallantoic membrane

The chick embryo chorioallantoic membrane (CAM) is commonly used in vivo to study both angiogenesis and anti‐angiogenesis. Rapid membrane water transport is mediated by a family of molecular water channels, called aquaporins (AQPs), which have been identified in the epithelial and endothelial cells of higher vertebrates. AQP1, expressed in adsorptive and secretory epithelia, is also expressed in endothelial cells of capillaries and arteries. Its mRNA has been found in vascular smooth muscle cells (VSMCs) of arteries and capillaries, as well as in a subset of VSMCs of human atherosclerotic plaques. This study investigated the developmental expression of AQP1 in the chick CAM by Western blot and immunohistochemistry. Western blot results show that a major nonglycosylated band was observed with electrophoretic mobility of approximately 28 kDa in the three developmental stages examined. Immunohistochemistry data demonstrate that AQP1 was clearly expressed in the ectodermal and endodermal epithelia, the vascular endothelium, and the VSMCs. Because little information is available on the behavior of microvessel AQP1 during angiogenesis in normal and pathological conditions, our data relative to the pattern of expression of AQP1 in CAM blood vessels in normal conditions may be considered a useful tool to further investigate its modifications in several experimental conditions implying a stimulation or an inhibition of angiogenesis in the CAM assay. Anat Rec 268:85–89, 2002. © 2002 Wiley‐Liss, Inc.     

Brain volume regulation: osmolytes and aquaporin perspectives

Cerebral water control is critical to maintain neuronal excitability, and to prevent injuries derived from brain swelling or shrinkage. The influence of aquaporins (AQPs) in the balance of water distribution between intracranial compartments is getting much experimental support. The importance of AQPs in fluid clearance during vasogenic brain edema seems well established but their role in cytotoxic swelling and in brain cell shrinkage is not known in detail. The main AQPs function as water channels anticipates their influence on cell volume changes as well as on the mechanisms of volume recovery, which include notably the osmolyte translocation across the cell membrane. Osmolyte fluxes permit the reestablishment of an osmotic balance and volume recovery in anisosmotic-elicited cell volume changes, but are also causal factors per se of brain cell swelling or shrinkage in pathological situations. This review aims to inform on the so far described functional interactions between AQPs and osmolyte fluxes and their volume-sensitive pathways. It also points to the coincidence of AQPs and activation of osmolyte fluxes in physiological and pathological conditions and to the importance of finding possible functional links between these two events, thus enlarging the possibilities via AQP manipulations, to prevent the adverse consequences of cell volume changes in brain.