Relationship between expression of tight junction-related molecules and perturbed epidermal barrier function in UVB-irradiated hairless mice

In epithelia, tight junctions (TJs) create a primary barrier to the diffusion of solutes through the paracellular pathway. Although TJ-related molecules are present in the epidermis, the precise mechanisms underlying TJ functions in this tissue remain unclear. In this study, we use an ultraviolet (UV) B-irradiated murine skin model, in which the epidermal barrier function has been perturbed, to demonstrate a correlation between the expression patterns of TJ-related molecules and the epidermal permeability of TJs. Occludin remained localized in the upper epidermis, regardless of UVB irradiation (0.15 J per cm²). ZO-1 was localized in the upper portion of normal epidermis, and within 3–4 days of UVB irradiation, it was expressed throughout the upper epidermis and their expression coincided with epidermal thickening. Protein expression of claudin-1 and occludin did not alter until 3 and 4 days after UVB irradiation, respectively and thereafter expression remained elevated above pre-irradiation levels. An in vivo epidermal permeability assay revealed that tight junction-barrier function was perturbed by UVB irradiation, whereby biotinylated markers clearly permeated the stratum granulosum 3–5 days after irradiation. These results suggest that TJ-related molecules play important roles in epidermal barrier function in murine skin and show that changes in their expression patterns are associated with epidermal barrier perturbation after UVB irradiation. Specifically, it appears that epidermal barrier recovery is accelerated by the increased production and dense localization of occludin in the cell–cell contact region of the stratum granulosum.     

肠上皮细胞紧密连接的生物学功能及在肠屏障中的作用

紧密连接是肠上皮细胞间的主要连接方式,对维持上皮细胞极性及调节肠屏障的通透性发挥着重要的作用.因此,维持肠上皮的完整性对于保护肠道屏障功能、防止细菌内毒素及毒性大分子物质进入体内具有重要意义.作者就紧密连接在肠上皮中的生物学功能、分子调控机制及影响因素作一综述,旨在为改善肠屏障功能提供有益的帮助.     

闭合蛋白在脑缺血中的作用

血脑屏障(blood-brain barrier, BBB)损伤是缺血性卒中的重要病理学改变.闭合蛋白是构成BBB紧密连接的主要组成部分,在维持BBB完整性中发挥着重要作用.脑缺血通过诱导炎性介质、活性氧和基质金属蛋白酶的激活,启动闭合蛋白降解,并使紧密连接-细胞骨架蛋白相互作用发生改变,导致BBB完整性破坏,通透性增高.文章主要阐述了闭合蛋白与BBB、脑水肿和出血性转化之间的关系以及闭合蛋白作为缺血性卒中干预靶点的可能性.     

含益生元肠内营养对重症急性胰腺炎大鼠肠紧密结合蛋白occludin的作用

目的探讨早期给予含益生元（低聚半乳糖）肠内营养（EN）对重症急性胰腺炎（SAP）大鼠肠紧密结合蛋白oecludin蛋白表达以及mRNA表达的作用。方法将64只SD大鼠随机分成8组（n=8）：假手术对照4d和7d组、SAP造模＋肠内营养（SAP＋EN）4d和7d组、SAP造模＋含益生元肠内营养（SAP＋PRE-EN）4d和7d组、SAP造模＋肠外营养（SAP4-PN）4d和7d组。胰腺被膜下均匀注射3．8％牛磺胆酸钠1ml建立SAP大鼠模型,采用免疫组织化学法检测occludin蛋白表达,实时荧光定量PCR法检测occludinmRNA含量。结果各SAP组oecludin蛋白表达和mRNA含量均显著低于假手术对照组（P〈0．01）,SAP＋EN组和SAP＋PRE-EN组显著高于SAP＋PN组（P〈0．05）,SAP＋PRE．EN组显著高于SAP＋EN组（P〈0．05）。Occludin蛋白表达和mRNA含量呈显著正相关（r=0．83,P〈0．01）。结论含益生元肠内营养可以增强肠黏膜紧密结合蛋白occludin的表达,其作用与上调occludinmRNA水平有关。     

Disruption of the blood–brain barrier in collagen-induced arthritic mice

Patients with rheumatoid arthritis (RA) are at higher risk of developing pathological cardiovascular and cerebrovascular events than non-RA subjects. Vascular endothelial dysfunction is involved in the induction of cardiovascular events and this process is also observed in patients with RA. Endothelial dysfunction impairs the integrity of the blood–brain barrier (BBB); this phenomenon also underlies brain damage in cerebrovascular diseases. This study was aimed at evaluating the influence of a chronic inflammatory state on BBB integrity in RA using collagen-induced arthritis (CIA), an animal model of RA. CIA was induced by intradermal injection of type II collagen emulsified with Freund's complete adjuvant at the base of the tail of DBA/1 mice. Cerebrovascular permeability was assessed by measurement of sodium fluorescein (Na–F) content in the brains of CIA mice. The expression level of tight junction proteins was investigated by immunoblotting and immunofluorescence of occludin and zonula occludens-1 (ZO-1). Cerebrovascular permeability to Na–F in the brain was increased in CIA mice. This CIA-induced BBB hyperpermeability was more remarkable in the advanced stage than that in the persistent stage of the arthritis. The expression of occludin, but not that of ZO-1, was decreased by CIA. Our results indicate that the integrity of the BBB could be impaired in the inflammatory pathophysiology of RA.     

Expression of claudins 1, 4, 5, and 7 and occludin, and relationship with prognosis in squamous cell carcinoma of the tongue

Claudins and occludin are tight junctional proteins known to play a role in normal tissues and epithelial tumors. We analyzed the distribution patterns of claudins 1, 4, 5, and 7 and occludin in the superficial and invasive front of squamous cell carcinoma of the tongue of 97 patients and their relationship to cause-specific (squamous cell carcinoma of the tongue) patient survival (median follow-up period of 33.5 months; range, 1-234 months). Claudins 1 and 7 were strongly expressed, claudin 4 had moderate expression, whereas claudin 5 was least expressed. Occludin staining was mostly negative or very weak. Western blot analysis of tongue carcinoma (HSC-3) cells showed that all these proteins are also expressed in vitro. In cause-specific survival analysis, strong and low immunoreactivity of claudin 7 tended to be associated with decreased survival compared with medium immunoreactivity. We suggest that analyzing the immunohistologic staining levels of claudin 7 could be used for the prognostic purposes in patients with tongue squamous cell carcinoma.     

NF-κB在重症急性胰腺炎小鼠肠黏膜屏障损伤中的作用

目的探讨NF-κB在重症急性胰腺炎小鼠肠黏膜屏障功能损伤中的调控机制。方法 36只BALB/C小鼠随机分为对照组、模型组、NF-κB干预组,每组12只。18h后处死小鼠,比较各组的腹腔内大体改变、肠黏膜病理改变,肠道通透性的变化及血清细胞因子水平,肠上皮紧密连接蛋白occludin的表达。结果模型组小鼠腹腔内呈明显炎症反应,肠管水肿,肠黏膜水肿,肠道通透性显著增高,NF-κB特异性阻断剂能降低肠道损伤,改善肠黏膜水肿,上调肠上皮紧密连接蛋白occludin的表达,显著降低肠道通透性,降低细胞因子水平。结论 NF-κB阻断剂能够通过选择性的抑制NF-κB活性,改善受损的肠屏障功能。这一作用通过上调肠上皮紧密连接蛋白occludin的水平而实现。     

紧密连接蛋白在人宫颈癌组织中的表达及其临床意义

目的分析紧密连接蛋白(Occludin)在人宫颈癌中的表达及其临床意义。方法选取40例宫颈癌患者为研究对象,用免疫印迹法检测Occludin蛋白在40对配对宫颈癌组织和正常组织中的表达情况,分析其蛋白表达与临床病理参数的相关性。结果在正常组织和癌组织中Occludin蛋白的低表达率分别为62.50%(25例/40例)和77.50%(31例/40例),高表达率分别为37.50%(15例/40例)和22.50%(9例/40例),Occludin蛋白的表达量分别为(0.39±0.34)和(0.11±0.11),差异均有统计学意义(均P<0.05)。Occludin蛋白表达水平与患者年龄、肿瘤大小、FIGO分期、病理分级、淋巴结转移等均无明显相关性(均P>0.05)。结论宫颈癌组织中Occludin蛋白呈异常低表达,可能参与了宫颈癌的发生与发展病理过程,但与患者临床病理特征无关。     

重症肝炎患者肠道屏障功能的变化

目的 研究重症肝炎患者肠道IgA、分泌片(SC)和ZO-1、occludin的变化,了解重症肝炎患者伴发腹部症状的原因.方法 采用免疫组化方法分别检测肠道IgA、SC和ZO-1、occludin.结果 与对照组比较,重症肝炎患者肠道IgA、SC和ZO-1、occludin染色明显减弱.结论 重症肝炎患者肠道IgA、SC和ZO-1、occludin表达下降,导致肠道屏障功能发生异常是引起腹部症状的原由之一.     

谷氨酰胺对急性肺损伤大鼠肺泡上皮屏障功能的影响

目的:观察谷氨酰胺对急性肺损伤大鼠肺泡上皮屏障功能及紧密连接(TJ)特征性蛋白occludin和黏附连接蛋白E-cadherin的影响。方法:40只SD大鼠随机分为对照组、谷氨酰胺处理组(Gln组)、内毒素处理组(LPS组)、谷氨酰胺并内毒素处理组(Gln+LPS组)。测定支气管肺泡渗透性、运用免疫印迹测定和RT-PCR测定肺泡Ⅱ型上皮细胞中occludin和E-cadherin的蛋白及mRNA表达。结果:内毒素导致支气管肺泡上皮渗透性明显增高2倍左右(P<0.01);补充谷氨酰胺可以明显改善由内毒素处理引起的支气管肺泡上皮渗透性增高(P<0.05),但Gln+LPS组支气管肺泡渗透性仍较对照组及Gln组增高(P<0.05)。免疫印迹和RT-PCR显示在LPS组的occludin和E-cadherin蛋白和mRNA表达水平均较对照组及Gln组的低(P<0.01);在Gln+LPS组中occludin和E-cadherin的蛋白和mRNA表达水平较LPS组的高(P<0.05),而较对照组及Gln组的表达水平低(P<0.05)。结论:实验提示内毒素通过降低TJ分子occludin和E-cadherin的mRNA、蛋白表达水平导致肺泡上皮屏障功能受损,补充谷氨酰胺通过上调其mRNA、蛋白表达水平而对肺泡上皮屏障功能有保护作用。