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101.
目的观察软骨保护剂氨基葡萄糖(GS)和硫酸软骨素(CS)对原发性骨关节炎(OA)模型雌性Hartley豚鼠膝关节软骨组织结构、组织成分以及血清中蛋白多糖含量的影响。方法120只2月龄雌性Hartley豚鼠,随机分为三个试验组和一个空白对照组。三个试验组分别为:1g/kg bw GS组,0.5g/kg bw CS组,GS1g/kg bw+CS0.5g/kg bw联合使用组和蒸馏水对照组。自由饮水给予受试物,连续5个月。分别于给药前,给药1个月、2个月、3个月、4个月和5个月后,每组各取5只动物膝关节进行组织病理学(HE染色)和组织化学(PAS、Alcian Blue、和Mallory染色)检查以及血清蛋白多糖含量的检测。结果病理及组化检查:对照组在实验开始1个月后软骨组织病理积分即不断增高;GS组在给药三个月后才开始上升;CS组在给药的5个月中病理积分增高缓慢,仅第4个月上升较明显;联合使用组在给药的5个月中病理积分一直没有增高,并且给药5个月后的病理积分显著低于同组给药前期的积分。血清蛋白多糖含量:给药4个月后,GS组,CS组和联合使用组血清中蛋白多糖含量下降减少,与各自同期对照组相比差异均有显著性(P<0.05)。结论氨基葡萄糖和硫酸软骨素对豚鼠原发性软骨组织退化的发生、发展,以及血清蛋白多糖含量的下降均有延缓及抑制作用。并且以两者的联合作用最强,显现出一定的修复作用。 相似文献
102.
Glypican-3 expression is markedly decreased in human gastric cancer but not in esophageal cancer 总被引:2,自引:0,他引:2
Zhu Z Friess H Kleeff J Wang L Wirtz M Zimmermann A Korc M Büchler MW 《American journal of surgery》2002,184(1):78-83
BACKGROUND: Deregulation of the expression of glypican-3, a heparan sulfate proteoglycan, has been demonstrated in several human cancers. METHODS: In the present study, glypican-3 mRNA expression was analyzed by Northern blotting and in situ hybridization in 20 normal and 41 cancerous esophageal specimens as well as in 15 normal and 32 cancerous gastric tissues. RESULTS: Glypican-3 mRNA was expressed in both normal and esophageal cancer tissues without a significant difference between normal and cancerous tissues, and without a correlation with histological type, tumor stage, tumor grade, or patient survival. Moderate to strong glypican-3 mRNA signals were found in the cytoplasm of squamous epithelial cells of the normal esophagus. In both squamous and adenocarcinomas of the esophagus glypican-3 mRNA signals were also moderately to strongly present in the cytoplasm of the cancer cells. In gastric tissues, glypican-3 mRNA was present in 53% of normal gastric tissue samples, but was below the detection level in all examined gastric cancer samples. Glypican-3 mRNA signals were moderately to strongly present in the cytoplasm of gastric mucosal epithelial cells, but were only very faintly present in some cancer cells. CONCLUSIONS: Glypican-3 may be involved in the growth control of normal esophageal and gastric epithelial cells. Furthermore, our results suggest that glypican-3 may play a tumor suppressor role in gastric but not in esophageal cancer. 相似文献
103.
We have investigated the hypothesis that the chemorepellent Semaphorin3A may be involved in the failure of axonal regeneration after injury to the ascending dorsal columns of adult rats. Following transection of the thoracic dorsal columns, fibroblasts in the dorsolateral parts of the lesion site showed robust expression of Semaphorin3A mRNA. In addition, dorsal root ganglion (DRG) neurons with projections through the dorsal columns to the injury site persistently expressed both Semaphorin3A receptor components, neuropilin-1 and plexin-A1. These ascending DRG collaterals failed to invade scar regions occupied by Semaphorin3A-positive fibroblasts, even in animals which had received conditioning lesions of the sciatic nerve to enhance regeneration. Other axon populations in the dorsal spinal cord were similarly unable to penetrate Semaphorin3A-positive scar tissue. These data suggest that Semaphorin3A may create an exclusion zone for regenerating dorsal column fibres and that enhancing the intrinsic regenerative response of DRG neurons has only limited effects on axonal regrowth. Tenascin-C and chondroitin sulphate proteoglycans were also detected at the injury site, which was largely devoid of central nervous system (CNS) myelin, showing that several classes of inhibitory factors, including semaphorins, with only partially overlapping spatial and temporal patterns of expression are in a position to participate in preventing regenerative axonal growth in the injured dorsal columns. Interestingly, conditioning nerve injuries enabled numerous ascending DRG axons to regrow across areas of strong tenascin-C and chondroitin sulphate proteoglycan expression, while areas containing Semaphorin3A and CNS myelin were selectively avoided by (pre)primed axonal sprouts. 相似文献
104.
Biosynthesis of proteoglycan in bone and cartilage of parathyroid hormone-related protein knockout mice 总被引:1,自引:0,他引:1
Ogihara Y Suda N Hammond VE Senior PV Beck F Yanagishita M 《Journal of bone and mineral metabolism》2001,19(1):4-12
Proteoglycans are suggested to regulate cell adhesion, differentiation and mineralization of hard tissues. In vitro studies
have shown that many humoral and local factors regulate proteoglycan synthesis. Among them, parathyroid hormone (PTH) and
parathyroid hormone-related protein (PTHrP) have potent stimulating effects on proteoglycan synthesis. However, the exact
role of PTHrP on the biosynthesis and metabolism of proteoglycans during skeletal development is not clear. To clarify this
point, we examined bony and cartilaginous explants of newborn mice with disrupted PTHrP alleles. Ribs of homozygous PTHrP-knockout
mice and wild-type littermates were dissected into bony and cartilaginous regions and metabolically labeled with [35S]sulfate in culture. Radiolabeled proteoglycans were analyzed by column chromatography. The elution profiles of [35S]-labeled proteoglycan from cartilaginous explants did not differ between homozygous PTHrP-knockout mice and wild-type littermates.
However, the amount of labeled proteoglycan in homozygous PTHrP-knockout mice was only 4%–5% that of wild-type littermates.
In contrast with cartilaginous explants, the amount of labeled proteoglycans in bony explants did not differ between the two
genotypes. Interestingly, besides the common major peak (Kd = 0.10–0.16) observed in the bony explants of both genotypes, a minor peak (Kd = 0.42) was specifically present in homozygous PTHrP-knockout mice. This minor peak was earlier than that of free glycosaminoglycan
(GAG) chains, suggesting that the core protein, but not GAG chain, was cleaved in the bony explants of homozygous PTHrP. These
findings demonstrate a crucial and nonredundant role of PTHrP in the regulation of proteoglycan synthesis and metabolism during
skeletal development.
Received: February 21, 2000 / Accepted: June 16, 2000 相似文献
105.
Proteoglycans: pericellular and cell surface multireceptors that integrate external stimuli in the mammary gland 总被引:4,自引:0,他引:4
Delehedde M Lyon M Sergeant N Rahmoune H Fernig DG 《Journal of mammary gland biology and neoplasia》2001,6(3):253-273
Proteoglycans consist of a core protein and an associated glycosaminoglycan (GAG)4 chain of heparan sulfate, chondroitin sulfate, dermatan sulfate or keratan sulfate, which are attached to a serine residue. The core proteins of cell surface proteoglycans may be transmembrane, e.g., syndecan, or GPI-anchored, e.g., glypican. Many different cell surface and matrix proteoglycan core proteins are expressed in the mammary gland and in mammary cells in culture. The level of expression of these core proteins, the structure of their GAG chains, and their degradation are regulated by many of the effectors that control the development and function of the mammary gland. Regulatory proteins of the mammary gland that bind GAG include many growth factors and morphogens (fibroblast growth factors, hepatocyte growth factor/scatter factor, members of the midkine family, wnts), matrix proteins (collagen, fibronectin, and laminin), enzymes (lipoprotein lipase) and microbial surface proteins. Structural diversity within GAG chains ensures that each protein-GAG interaction is as specific as necessary and a number of sequences of saccharides that recognize individual proteins have been elucidated. The GAG-protein interactions serve to regulate the signal output of growth factor receptor tyrosine kinase and hence cell fate as well as the storage and diffusion of extracellular protein effectors. In addition, GAGs clearly coordinate stromal and epithelial development, and they are active participants in mediating cell-cell and cell-matrix interactions. Since a single proteoglycan, even if it carries a single GAG chain, can bind multiple proteins, proteoglycans are also likely to act as multireceptors which promote the integration of cellular signals. 相似文献
106.
Perineuronal nets (PNs) are known as chondroitin sulfate-rich, lattice-like coatings of the extracellular matrix ensheathing mainly GABAergic, parvalbumin-containing neurons especially in the cerebral cortex. PNs have also been detected around GABA-immunonegative cells which were shown to be not aminergic, cholinergic, nitrinergic or peptidergic in various brain regions of some mammalian species. To find out whether glycine and aspartate may occur in net-bearing neurons the present study was focused on the rat medial nucleus of the trapezoid body (MNTB) which contains a large portion of cells immunoreactive for these amino acids, but appears to be devoid of GABA-immunoreactive cell bodies. PNs were detected around many glycine- and aspartate-immunopositive neurons in the MNTB by carbocyanine double labeling and confocal laser scanning microscopy. An additional finding was that the lectin-cytochemically stained extracellular matrix surrounds the calretinin-immunoreactive calyces of Held known as giant glutamatergic endbulbs which cover glycinergic principal cells in the MNTB. As elucidated by triple fluorescence labeling, the vast majority of somata co-expressed the calcium-binding proteins parvalbumin and calbindin, but not calretinin. The observed co-localization of PNs and immunoreactivity for the voltage-dependent potassium channel Kv3.1b - as an established marker of fast-firing parvalbumin-containing neurons - supports the assumed function of PNs as a cation exchanger ensuring rapid ion transport as required by highly active nerve cells. 相似文献
107.
In vitro and in vivo protective effects of proteoglycan isolated from mycelia of Ganoderma lucidum on carbon tetrachloride-induced liver injury 总被引:3,自引:0,他引:3
Yang XJ Liu J Ye LB Yang F Ye L Gao JR Wu ZH 《World journal of gastroenterology : WJG》2006,12(9):1379-1385
AIM: To investigate the possible mechanism of the protective effects of a bioactive fraction,Ganoderma lucidum proteoglycan (GLPG) isolated from Ganoderma lucidum mycelia, against carbon tetrachloride-induced liver injury. METHODS: A liver injury model was induced by carbon tetrachloride. Cytotoxicity was measured by MTT assay.The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined with an automatic multifunction-biochemical analyzer and the levels of superoxide dismutase (SOD)and TNF-alpha were determined following the instructions of SOD kit and TNF radioimmunoassay kit. Liver sections were stained with hematoxylin and eosin (H and E) for histological evaluation and examined under light microscope. RESULTS: We found that GLPG can alleviate the L-02 liver cells injury induced by carbon tetrachloride (CCl4) through the measurements of ALT and AST activities and the administration of GLPG to L-02 cells did not display any toxicity. Furthermore, histological analysis of mice liver injury induced by CCl4 with or without GLPG pretreatment indicated that GLPG can significantly suppress the toxicity induced by CCl4 in mice liver. We also found that GLPG reduced TNF-alpha level induced by CCl4 in the plasma of mice, whereas increased SOD activity in the rat serum. CONCLUSION: GLPG has hepatic protective activity against CCl4-induced injury both in vitro and in vivo. The possible anti-hepatotoxic mechanisms may be related to the suppression of TNF-alpha level and the free radical scavenging activity. 相似文献
108.
Carulli D Rhodes KE Brown DJ Bonnert TP Pollack SJ Oliver K Strata P Fawcett JW 《The Journal of comparative neurology》2006,494(4):559-577
The decrease in plasticity that occurs in the central nervous system during postnatal development is accompanied by the appearance of perineuronal nets (PNNs) around the cell body and dendrites of many classes of neuron. These structures are composed of extracellular matrix molecules, such as chondroitin sulfate proteoglycans (CSPGs), hyaluronan (HA), tenascin-R, and link proteins. To elucidate the role played by neurons and glial cells in constructing PNNs, we studied the expression of PNN components in the adult rat cerebellum by immunohistochemistry and in situ hybridization. In the deep cerebellar nuclei, only large excitatory neurons were surrounded by nets, which contained the CSPGs aggrecan, neurocan, brevican, versican, and phosphacan, along with tenascin-R and HA. Whereas both net-bearing neurons and glial cells were the sources of CSPGs and tenascin-R, only the neurons expressed the mRNA for HA synthases (HASs), cartilage link protein, and link protein Bral2. In the cerebellar cortex, Golgi neurons possessed PNNs and also synthesized HASs, cartilage link protein, and Bral2 mRNAs. To see whether HA might link PNNs to the neuronal cell surface by binding to a receptor, we investigated the expression of the HA receptors CD44, RHAMM, and LYVE-1. No immunolabelling for HA receptors on the membrane of net-bearing neurons was found. We therefore propose that HASs, which can retain HA on the cell surface, may act as a link between PNNs and neurons. Thus, HAS and link proteins might be key molecules for PNN formation and stability. 相似文献
109.
Glypican-3, overexpressed in hepatocellular carcinoma,modulates FGF2 and BMP-7 signaling 总被引:11,自引:0,他引:11
Midorikawa Y Ishikawa S Iwanari H Imamura T Sakamoto H Miyazono K Kodama T Makuuchi M Aburatani H 《International journal of cancer. Journal international du cancer》2003,103(4):455-465
The Glypican (GPC) family is a prototypical member of the cell-surface heparan sulfate proteoglycans (HSPGs). The HSPGs have been demonstrated to interact with growth factors, act as coreceptors and modulate growth factor activity. Here we show that based on oligonucleotide array analysis, GPC3 was upregulated in hepatocellular carcinoma (HCC). By northern blot analysis, GPC3 mRNA was found to be upregulated in 29 of 52 cases of HCC (55.7%). By Western blot analysis carried out with a monoclonal anti-GPC3 antibody we generated, the GPC3 protein was found to be overexpressed in 6 hepatoma cell lines, HepG2, Hep3B, HT17, HuH6, HuH7 and PLC/PRF/5, as well as 22 tumors (42.3%). To investigate the role of overexpressed GPC3 in liver cancer, we analyzed its effects on cell growth of hepatoblastoma-derived cells. Overexpression of GPC3 modulated cell proliferation by inhibiting fibroblast growth factor 2 (FGF2) and bone morphogenetic protein 7 (BMP-7) activity. An interaction of GPC3 and FGF2 was revealed by co-immunoprecipitation, while GPC3 was found to inhibit BMP-7 signaling through the Smad pathway by reporter gene assay. The modulation of growth factors by GPC3 may help explain its role in liver carcinogenesis. In addition, the ability of HCC cells to express GPC3 at high levels may serve as a new tumor marker for HCC. 相似文献
110.
Extracellular matrix synthesis and ultrastructural changes of degenerative disc cells transfected by Ad/CMV-hTGF-β1 总被引:14,自引:0,他引:14
Objective To determine whether the synthesis of proteoglycan, collagen and associated ultrastructure are related to the adenovirus-mediated gene transferred to adult degenerative cells.Methods Adenovirus/cytomegalovirus human transforming growth fector-β1 (Ad/CMV-hTGF-β1) was used to transfect degenerative cells. Antonopulos method, Miamine method and transmission electrion microscopy were conducted to study the synthesis of proteoglycan, collagen, and ultrastructure, respectively. Cell cultures were established from the nucleus pulpous and annulus fibrosus tissues, which were taken from surgery.Results Nucleus pulpous and annulus fibrosus cells were efficiently transduced by the adenoviral vector carrying hTGF-β1 gene. The synthesis of proteoglycan and collagen increased compared with the control group (P<0.05). The metabolism of cells was slightly improved. No significant toxic effects were found.Conclusions Expression of hTGF-β1 gene is efficient to accelerates proteoglycan synthesis and thus accelerates the improvement of collagen. The function and structure of degenerative cells are improved. Ad/CMV-hTGF-β1 may be suitable for treating disc degeneration. 相似文献