Mechanical strain enhances proteoglycan message in fibroblasts from asthmatic subjects

BACKGROUND: Remodelling of the asthmatic airway includes increased deposition of proteoglycan (PG) molecules. One of the stimuli driving airway remodelling may be excessive mechanical stimulation. OBJECTIVE: We hypothesized that fibroblasts from asthmatic patients would respond to excessive mechanical strain with up-regulation of message for PGs. METHODS: We obtained fibroblasts from asthmatic patients (AF) and normal volunteers (NF) using endobronchial biopsy. Cells were maintained in culture until the fifth passage and then grown on a flexible collagen-coated membrane. Using the Flexercell device, cells were then subjected to cyclic stretch at 30% amplitude at 1 Hz for 24 h. Control cells were unstrained. Total RNA was extracted from the cell layer and quantitative RT-PCR performed for decorin, lumican and versican mRNA. RESULTS: In unstrained cells, the expression of decorin mRNA was greater in AF than NF. With strain, NF showed increased expression of versican mRNA and AF showed increased expression of versican and decorin mRNA. The relative increase in versican mRNA expression with strain was greater in AF than NF. CONCLUSIONS: These data support the hypothesis that proteoglycan message is increased in asthmatic fibroblasts subject to mechanical strain. This finding has implications for the mechanisms governing airway wall remodelling in asthma.     

Lumican对角膜SLRPs家族成员及角膜透明性的影响

Lumican作为小分子亮氨酸重复蛋白聚糖(SLRPs)中的主要成员,在角膜基质层生成过程中起重要作用.SLRPs大量存在于角膜基质层中,包括I型:decorin和biglycan, II型:lumican,keratocan和fibromodulin.成员之间合作调控角膜基质层原纤维的形成、成熟及装配,从而形成基质层高度有序的结构特点,这是形成和维持角膜透明性的基础.Lumican基因表达改变会影响lumican和其他细胞外基质成分在角膜中的正常比例和排列关系,影响细胞外基质间的相互作用,进而导致胶原原纤维形成和成熟异常,最终造成角膜基质层混浊.     

miR-33a通过下调lumican基因抑制结肠癌细胞的侵袭和迁移

目的:探讨不同级别结肠癌中miR-33a和基膜聚糖(lumican)基因的表达情况,同时研究miR-33a对于结肠癌细胞侵袭和迁移的影响.方法:收集2015年1月至2016年1月新乡医学院第一附属医院肿瘤科收治的141例结肠癌患者,Western blotting和qPCR检测不同级别结肠癌组织中miR-33a和lumican的表达情况.使用miR-33a mimic转染人结肠癌细胞SW480,qPCR检测miR-33a mimic转染后细胞miR-33a和lumican mRNA的表达变化情况,使用Transwell侵袭实验检测miR-33a对人结肠癌细胞SW480侵袭能力的影响,使用划痕实验检测miR-33a对人结肠癌细胞SW480迁移能力的影响.裸鼠皮下成瘤实验检测miR-33a对结肠癌移植瘤生长以及裸鼠生存的影响.结果:随着结肠癌肿瘤级别的增加,miR-33a表达明显降低,而lumican表达水平明显增加;随着结肠癌病理分期和分级的增加,miR-33a表达逐渐降低;淋巴结转移的结肠癌组织中miR-33a的表达明显降低.转染miR-33a-mimic可以明显上调miR-33a的表达,上调miR-33a可以显著降低lumican蛋白表达水平、可以抑制结肠癌细胞的侵袭和迁移能力.miR-33a-mimic组荷瘤裸鼠肿瘤增长幅度明显减慢,而荷瘤裸鼠生存期明显延长.结论:miR-33a与结肠癌分期、分级以及是否有淋巴结转移有关,miR-33a可通过下调lumican抑制结肠癌细胞的侵袭和迁移.     

Effect of morpholino antisense oligonucleotide against lumican mRNA in human embryonic kidney (HEK) 293 cells

Lumican is a member of the small-leucine-rich proteoglycan (SLRP) family and is overexpressed during wound healing of the cornea, in ischemic and reperfused heart, and in several cancer tissues. Lumican is considered to regulate the collagen fibril diameter and interfibrillar spacing. However, the effect of lumican on cell growth has not been adequately examined. In the present study, we attempted to clarify whether lumican contributes to human embryonic kidney (HEK) 293 cell growth, using the morpholino antisense oligonucleotide (m-anti oligo) against lumican mRNA. M-anti oligo is a novel oligonucleotide and exhibits a higher antisense activity, higher water solubility, and greater resistance to nucleases in target cells than phosphorothioate types of oligonucleotide. After delivery of m-anti oligo against lumican mRNA, the fluorescein 5-isothiocyanate (FITC) conjugated oligonucleotides were observed in the cytoplasm and nucleus of HEK 293 cells at 24 h by confocal laser microscopy. M-anti oligo for lumican mRNA strongly inhibited the synthesis of lumican protein in the HEK 293 cells, and the HEK cell growth rate was higher than those in the control groups. These findings may indicate that lumican protein has an inhibitory effect on HEK 293 cell growth in vitro .     

The small leucine‐rich repeat proteoglycans in tissue repair and atherosclerosis

Proteoglycans consist of a protein core with one or more covalently attached glycosaminoglycan (GAG) side chains and have multiple roles in the initiation and progression of atherosclerosis. Here we discuss the potential and known functions of a group of small leucine‐rich repeat proteoglycans (SLRPs) in atherosclerosis. We focus on five SLRPs, decorin, biglycan, lumican, fibromodulin and PRELP, because these have been detected in atherosclerotic plaques or demonstrated to have a role in animal models of atherosclerosis. Decorin and biglycan are modified post‐translationally by substitution with chondroitin/dermatan sulphate GAGs, whereas lumican, fibromodulin and PRELP have keratan sulphate side chains, and the core proteins have leucine‐rich repeat (LRR) motifs that are characteristic of the LRR superfamily. The chondroitin/dermatan sulphate GAG side chains have been implicated in lipid retention in atherosclerosis. The core proteins are discussed here in the context of (i) interactions with collagens and their implications in tissue integrity, fibrosis and wound repair and (ii) interactions with growth factors, cytokines, pathogen‐associated molecular patterns and cell surface receptors that impact normal physiology and disease processes such as inflammation, innate immune responses and wound healing (i.e. processes that are all important in plaque development and progression). Thus, studies of these SLRPs in the context of wound healing are providing clues about their functions in early stages of atherosclerosis to plaque vulnerability and cardiovascular disease at later stages. Understanding of signal transduction pathways regulated by the core protein interactions is leading to novel roles and therapeutic potential for these proteins in wound repair and atherosclerosis.     

Development of myotendinous‐like junctions that anchor cardiac valves requires fibromodulin and lumican

Results : FMOD deficient mice and double deficient FMOD; LUM mice exhibited anomalies in regions where cardiac valve tissue interdigitates with adjacent muscle for support. Ectopic connective and/or myocardial tissue(s) was associated with the more severe cardiac valve anomalies in FMOD; LUM deficient mice. At postnatal day 0 (P0) there was an increase in the mesenchymal cell number in the regions where valve cusps anchor in FMOD; LUM deficient mice compared to WT. The cardiac valve anomalies correlated with the highest levels of FMOD expression in the heart and also where myotendinous junctions (MTJ) components biglycan, collagen type I alpha 1, and collagen type VI, are also localized. 相似文献   

Visual function and higher order aberration after implantation of aspheric and spherical multifocal intraocular lenses:a meta-analysis

AIM: To assess the visual outcomes of aspheric multifocal intraocular lenses (IOLs) compared with spherical multifocal IOL after cataract surgery.METHODS:Potential prospective controlled trials that comparing aspheric multifocal IOL implantation with spherical multifocal IOL group were extracted from the computer database. The statistical analysis was carried out using Stata 10 software. Standardized mean differences with 95% confidence intervals (CIs) were calculated for continuous variables. The pooled estimates were computed in the use of a random-effects model.RESULTS:A systematic review identified five prospective nonrandomized controlled trials, including 178 aspheric multifocal IOL and 164 spherical multifocal IOL. There was no significant difference in uncorrected distance visual acuity (95%CI, -0.248 to 0.152;P=0.641) and uncorrected near visual acuity (95%CI, -0.210 to 0.428;P=0.504) between aspheric multifocal IOL and spherical multifocal IOL. Statistically significant differences were detected less spherical aberration in aspheric multifocal IOL (95%CI, -1.111 to -0.472; P＜0.001) when compared to spherical multifocal IOL. Spherical multifocal IOL showed a greater higher order aberration compared to the aspheric multifocal IOL (95%CI, -1.024 to-0.293; P＜0.001). Sensitivity analysis suggested that the results were relatively reliable.CONCLUSION:The overall findings indicated that aspheric multifocal IOL and spherical multifocal IOL provided similar visual acuity at near and distance. Patients implanted with aspheric multifocal IOL had less spherical aberration and higher order aberration than patients with spherical multifocal IOL. Further well-organized, prospective controlled trials involving larger patient numbers are needed.