Galectin-14 promotes hepatocellular carcinoma tumor growth via enhancing heparan sulfate proteoglycan modification

Hepatocellular carcinoma(HCC)is a highly heterogeneous malignancy and lacks effective treatment.Bulk-sequencing of different gene transcripts by comparing HCC tissues and adjacent normal tissues provides some clues for investigating the mechanisms or identifying potential targets for tumor progression.However,genes that are exclusively expressed in a subpopulation of HCC may not be enriched or detected through such a screening.In the current study,we performed a single cell-clone-based screening and identified galectin-14 as an essential molecule in the regulation of tumor growth.The aberrant expression of galectin-14 was significantly associated with a poor overall survival of liver cancer patients with database analysis.Knocking down galectin-14 inhibited the proliferation of tumor growth,whereas overexpressing galectin-14 promoted tumor growth in vivo.Non-targeted metabolomics analysis indicated that knocking down galectin-14 decreased glycometabolism;specifically that glycoside synthesis was significantly changed.Further study found that galectin-14 promoted the expression of cell surface heparan sulfate proteoglycans(HSPGs)that functioned as co-receptors,thereby increasing the responsiveness of HCC cells to growth factors,such as epidermal growth factor and transforming growth factor-alpha.In conclusion,the current study identifies a novel HCC-specific molecule galectin-14,which increases the expression of cell surface HSPGs and the uptake of growth factors to promote HCC cell proliferation.

Photobiomodulation inhibits the expression of chondroitin sulfate proteoglycans after spinal cord injury via the Sox9 pathway

Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins such as chondroitin sulfate proteoglycans inside and around the glial scar is known to affect axonal growth and be a major obstacle to autogenous repair.These proteins are thus candidate targets for spinal cord injury therapy.Our previous studies demonstrated that 810 nm photo biomodulation inhibited the formation of chondroitin sulfate proteoglycans after spinal cord injury and greatly improved motor function in model animals.However,the specific mechanism and potential targets involved remain to be clarified.In this study,to investigate the therapeutic effect of photo biomodulation,we established a mouse model of spinal cord injury by T9 clamping and irradiated the injury site at a power density of 50 mW/cm~2 for 50 minutes once a day for 7 consecutive days.We found that photobiomodulation greatly restored motor function in mice and down regulated chondroitin sulfate proteoglycan expression in the injured spinal cord.Bioinformatics analysis revealed that photobiomodulation inhibited the expression of proteoglycan-related genes induced by spinal cord injury,and versican,a type of proteoglycan,was one of the most markedly changed molecules.Immunofluorescence staining showed that after spinal cord injury,versican was present in astrocytes in spinal cord tissue.The expression of versican in primary astrocytes cultured in vitro increased after inflammation induction,whereas photobiomodulation inhibited the expression of ve rsican.Furthermore,we found that the increased levels of p-Smad3,p-P38 and p-Erk in inflammatory astrocytes were reduced after photobiomodulation treatment and after delivery of inhibitors including FR 180204,(E)-SIS3,and SB 202190.This suggests that Sma d 3/Sox9 and MAP K/Sox9 pathways may be involved in the effects of photobiomodulation.In summary,our findings show that photobiomodulation modulates the expression of chondroitin sulfate proteoglycans,and versican is one of the key target molecules of photo biomodulation.MAPK/Sox9 and Smad3/Sox9 pathways may play a role in the effects of photo biomodulation on chondroitin sulfate proteoglycan accumulation after spinal cord injury.

M1-type microglia can induce astrocytes to deposit chondroitin sulfate proteoglycan after spinal cord injury

After spinal cord injury(SCI),astrocytes gradually migrate to and surround the lesion,depositing chondroitin sulfate proteoglycan-rich extracellular matrix and forming astrocytic scar,which limits the spread of inflammation but hinders axon regeneration.Meanwhile,microglia gradually accumulate at the lesion border to form microglial scar and can polarize to generate a pro-inflammatory M1 phenotype or an anti-inflammatory M2 phenotype.However,the effect of microglia polarization on astrocytes is unclear.Here,we found that both microglia(CX3 CR1^(+))and astrocytes(GFAP^(+))gathered at the lesion border at 14 days post-injury(dpi).The microglia accumulated along the inner border of and in direct contact with the astrocytes.M1-type microglia(i NOS^(+)CX3 CR1^(+))were primarily observed at 3 and 7 dpi,while M2-type microglia(Arg1^(+)CX3 CR1^(+))were present at larger numbers at 7 and 14 dpi.Transforming growth factor-β1(TGFβ1)was highly expressed in M1 microglia in vitro,consistent with strong expression of TGFβ1 by microglia in vivo at 3 and 7 dpi,when they primarily exhibited an M1 phenotype.Furthermore,conditioned media from M1-type microglia induced astrocytes to secrete chondroitin sulfate proteoglycan in vitro.This effect was eliminated by knocking down sex-determining region Y-box 9(SOX9)in astrocytes and could not be reversed by treatment with TGFβ1.Taken together,our results suggest that microglia undergo M1 polarization and express high levels of TGFβ1 at 3 and 7 dpi,and that M1-type microglia induce astrocytes to deposit chondroitin sulfate proteoglycan via the TGFβ1/SOX9 pathway.The study was approved by the Institutional Animal Care and Use Committee of Anhui Medical University,China(approval No.LLSC20160052)on March 1,2016.

Effect of chondroitin sulfate proteoglycans on neuronal cell adhesion, spreading and neurite growth in culture

As one major component of extracellular matrix （ECM） in the central nervous system, chondroitin sul- fate proteoglycans （CSPGs） have long been known as inhibitors enriched in the glial scar that prevent axon regeneration after injury. Although many studies have shown that CSPGs inhibited neurite out- growth in vitro using different types of neurons, the mechanism by which CSPGs inhibit axonal growth remains poorly understood. Using cerebellar granule neuron （CGN） culture, in this study, we evaluated the effects of different concentrations of both immobilized and soluble CSPGs on neuronal growth, in- cluding cell adhesion, spreading and neurite growth. Neurite length decreased while CSPGs concentration arised, meanwhile, a decrease in cell density accompanied by an increase in cell aggregates formation was observed. Soluble CSPGs also showed an inhibition on neurite outgrowth, but it required a higher concen- tration to induce cell aggregates formation than coated CSPGs. We also found that growth cone size was significantly reduced on CSPGs and neuronal cell spreading was restrained by CSPGs, attributing to an inhibition on lamellipodial extension. The effect of CSPGs on neuron adhesion was further evidenced by interference reflection microscopy （IRM） which directly demonstrated that both CGNs and cerebral cortical neurons were more loosely adherent to a CSPG substrate. These data demonstrate that CSPGs have an effect on cell adhesion and spreading in addition to neurite outgrowth.

Role of chondroitin sulfate proteoglycan signaling in regulating neuroinflammation following spinal cord injury

Spinal cord injury （SCI） elicits a robust inflammatory response that is a hallmark of the secondary injury mechanisms. Neuroinflammation is orchestrated initially by the response of resident astrocytes and microglia to injury, which subsequently facilitates the recruitment of peripheral immune cells into the SCI lesion （Orr and Gensel, 2018）. This inflammatory response contributes to cell death and tissue degeneration through the production of pro-inflammatory cytokines and chemokines, free radicals and proteolytic enzymes. However, neuroinflammatory cells also play beneficial regulatory role in repair mechanisms after SCI by adopting a reparative and wound healing phenotype （Orr and Gensel, 2018; Tran et al., 2018）. Hence, understanding the underlying mechanisms by which immune cells are reg- ulated within the microenvironment of injury would aid in harnessing the reparative potential of inflammation following SCI.

Polymorphisms in ghrelin and heparan sulfate proteoglycan genes and their association with diabetic nephropathy in Pakistani population

Diabetic nephropathy(DN),a long term complication of diabetes,is the most common cause of end-stage renal disease,increasing the risk of death.Genetic predispositions play an important role in determining the susceptibility of the development of DN.Heparan sulphate proteoglycan(HSPG) and ghrelin(GH) gene polymorphisms are associated with the risk of DN.T allele frequency of the HSPG gene determined by BamHI polymorphism located in intron 6 may be a risk factor for the development of renal dysfunction in DN(Fisher two tailed test,CI = 95%,d.f.= 29,P = 0.016).The ghrelin gene polymorphism is caused by a cytosine-to-adenine transition in exon 2 of the preproghrelin gene forming Leu72Met variant.In Pakistani population,the preproghrelin Leu72Met polymorphism was observed to be not associated with diabetic nephropathy in patients as indicated by statistical analysis(CI = 95%,d.f.= 29,P = 0.691).The allelic frequencies of HSPG genetic polymorphism has the potential to be used as diagnostic markers for diabetic nephropathy disease.

Role of duck plague virus glycoprotein C in viral adsorption:Absence of specific interactions with cell surface heparan sulfate

Many mammalian herpes viruses utilize heparan sulfate （HS） moieties present on cell surface proteoglycans as receptors for cell entry, and this process also requires viral glycoprotein C （gC） homologues. However, our understanding of the role of gC in facilitating attachment of other alpha-herpes viruses such as the duck plague virus （DPV） remains preliminary. To study the role of gC during DPV infection, we used a gC-deleted mutant virus （DPV-AgC-EGFP）. Examination of the viral copy number by real-time PCR, as well as time course studies of viral adsorption and proliferation revealed that gC was involved in the viral binding to the cell surface. The affinity of viral glycoproteins （gB-DPV, gC-DPV, and gE-DPV） to HS was assessed using a prokaryotic expression system and HJTrapTM HeparJn HP column chromatography. In addition, to confirm that gC played a role in the interaction between DPV and HS, viruses were treated with the HS analogue heparin and host cells were treated with its inhibitors heparinase prior to exposure to DPV-△gC-EGFP or wild-type strain Chinese virulent duck plague virus （DPV-CHv）. The effects of heparin and heparinase on virus infectivity demonstrated that function of gC on Viral adsorption is independent of interactions between gC and heparin sulfate on cell surface. All in all, this study demonstrated that the gC of DPV can mediate viral adsorption in an HS-independent manner, which distinguish it from the gC of some other alpha-herpes viruses. Future studies will be required to identify the receptors involved in gC protein binding to cells. This work provides us a foundation for further studies of examining the roles of gC in the adsorption during duck plague virus infection.

The Importance of Heparan Sulfate in Herpesvirus Infection

Herpes simplex virus type-1 (HSV-1) is one of many pathogens that use the cell surface glycosaminoglycan heparan sulfate as a receptor. Heparan sulfate is highly expressed on the surface and extracellular matrix of virtually all cell types making it an ideal receptor. Heparan sulfate interacts with HSV-1 envelope glycoproteins gB and gC during the initial attachment step during HSV-1 entry. In addition,a modified form of heparan sulfate,known as 3-O-sulfated heparan sulfate,interacts with HSV-1 gD to induce fusion between the viral envelope and host cell membrane. The 3-O-sulfation of heparan sulfate is a rare modification which occurs during the biosynthesis of heparan sulfate that is carried out by a family of enzymes known as 3-O-sulfotransferases. Due to its involvement in multiple steps of the infection process,heparan sulfate has been a prime target for the development of agents to inhibit HSV entry. Understanding how heparan sulfate functions during HSV-1 infection may not only be critical for inhibiting infection by this virus,but it may also be crucial in the fight against many other pathogens as well.

Methylprednisolone Inhibits the Expression of Glial Fibrillary Acidic Protein and Chondroitin Sulfate Proteoglycans in Reactivated Astrocytes

创伤后的神经胶质增生导致硫酸软骨素蛋白聚糖(CSPG)的显著表达,从而抑制轴突生长和再生。甲基强地松龙(MP),一种合成的糖皮质激素,在急性脊髓损伤(SCI)的治疗中有神经保护作用和抗炎效应。但是,MP对于CSPG在活性胶质细胞中的表达的作用尚不清楚。本文用a-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯(AM-PA)诱导星形胶质细胞再活化,用环噻嗪模拟SCI的兴奋性中毒刺激。AMPA治疗后,星形胶质细胞再活化的标志物-胶质纤维酸性蛋白(GFAP)、CSPG神经聚糖和磷酸盐的表达都显著上调。AMPA治疗星形胶质细胞的条件培养液强烈抑制大鼠背根神经节中神经元的轴突生长,但这种作用能被MP的预处理所逆转。此外,MP下调成年SCI大鼠中GFAP和CSPG的表达,对抗RU486的糖皮质激素受体(GR)和GR si RNA能逆转MP对GFAP和神经聚糖表达的抑制作用。这些结果提示,MP能在兴奋性中毒损伤后通过GR介导的星形胶质细胞再活化下调和GSPG表达抑制来改善神经修复,促进轴突生长。

How does Cellular Heparan Sulfate Function in Viral Pathogenicity?

Heparan sulfate （HS） is ubiquitously expressed on the surfaces and in the extracellular matrix of virtually all cell types, making it an ideal receptor for viral infection. Compared with wild‐type viruses, cell culture‐adapted laboratory strains exhibit more efficient binding to cellular HS receptors. HS‐binding viruses are typically cleared faster from the circulation and cause lower viremia than their non‐HS‐binding counterparts, suggesting that the HS‐binding phenotype is a tissue culture adaptation that lowers virus fitness in vivo. However, when inoculated intracranially, efficient cell attachment through HS binding can contribute to viral neurovirulence. The primary aim of this review is to discuss the roles of HS binding in viral pathogenicity, including peripheral virulence and neurovirulence. Understanding how heparan sulfate functions during virus infection in vivo may prove critical for elucidating the molecular mechanism of viral pathogenesis, and may contribute to the development of therapeutics targeting HS.

Effects of Ligustrazine on Expression of Bone Marrow Heparan Sulfates in Syngeneic Bone Marrow Transplantation Mice

To explore the effects of ligustrazine on bone marrow heparan sulfates (HS) expression in bone marrow transplantation (BMT) mice, the syngeneic BMT mice were orally given 2 mg ligustrazine twice a day. On the 7th, 10th, 14th, 18th day after BMT, peripheral blood cells and bone marrow nuclear cells (BMNC) were counted, and the expression levels of HS in bone marrow and on the stromal cell surfaces were detected by immunohistochemistry and flow cytometry assay respectively. In ligustrazine-treated group, the white blood cells (WBC) and BMNC on the 7th, 10th, 14th, 18th day and platelets (PLT) on the 7th, 10th day were all significantly more than those in control group (P<0.05). The bone marrow HS expression levels in ligustrazine-treated group were higher than those in control group (P<0.05) on the 7th, 10th, 14th, 18th day. However, the HS expression levels on the stromal cell surfaces showed no significant difference between the two groups on the 18th day (P>0.05). It was concluded that ligustrazine could up-regulate HS expression in bone marrow, which might be one of the mechanisms contributing to ligustrazine promoting hematopoietic reconstitution after BMT.

Effects of Platelet Factor 4 on Expression of Bone Marrow Heparan Sulfate in Syngenic Bone Marrow Transplantation Mice

To explore the effects of platelet factor 4(PF4) on hematopoietic reconstitution and its mechanism in syngenic bone marrow transplantation (BMT). The syngenic B MT mice models were established. 20 and 26 h before irradiation, the mice were injected 20 μg/kg PF4 or PBS twice into abdominal cavity, then the donor bone marrow nuclear cells (BMNC) were transplanted. On the 7th day, spleen clone forming units (CFU S) were counted. On the 7th, 14th and 21st day after BMT, the BMNC and megakaryoryocytes in bone marrow tissue were counted and the percentage of hematopoietic tissue and expression level of heparan sulfate in bone marrow tissue were assessed. In PF4 treated groups, the CFU S counts on the 7th day were higher than those in BMT groups after BMT. The BMNC and megakaryoryocyte counts and the percentage of hematopoietic tissue and heparan sulfate expression level were higher than those in BMT group on the 7th, 14th and 21st day after BMT ( P <0.01 or P <0.05). PF4 could accelerate hematopoietic reconstitution of syngenic bone marrow transplantation. The promotion of the heparan sulfate expression in bone marrow may be one of mechanisms of PF4.

A tumor-associated heparan sulfate-related glycosaminoglycan promotes the generation of functional regulatory T cells

Functional Tregs play a key role in tumor development and progression,representing a major barrier to anticancer immunity.The mechanisms by which Tregs are generated in cancer and the influence of the tumor microenvironment on these processes remain incompletely understood.Herein,by using NMR,chemoenzymatic structural assays and a plethora of in vitro and in vivo functional analyses,we demonstrate that the tumoral carbohydrate A10(Ca10),a cell-surface carbohydrate derived from Ehrlich’s tumor(ET)cells,is a heparan sulfate-related proteoglycan that enhances glycolysis and promotes the development of tolerogenic features in human DCs.Ca10-stimulated human DCs generate highly suppressive Tregs by mechanisms partially dependent on metabolic reprogramming,PD-L1,IL-10,and IDO.Ca10 also reprograms the differentiation of human monocytes into DCs with tolerogenic features.In solid ET-bearing mice,we found positive correlations between Ca10 serum levels,tumor size and splenic Treg numbers.Administration of isolated Ca10 also increases the proportion of splenic Tregs in tumor-free mice.Remarkably,we provide evidence supporting the presence of a circulating human Ca10 counterpart(Ca10H)and show,for the first time,that serum levels of Ca10H are increased in patients suffering from different cancer types compared to healthy individuals.Of note,these levels are higher in prostate cancer patients with bone metastases than in prostate cancer patients without metastases.Collectively,we reveal novel molecular mechanisms by which heparan sulfate-related structures associated with tumor cells promote the generation of functional Tregs in cancer.The discovery of this novel structural-functional relationship may open new avenues of research with important clinical implications in cancer treatment.

Drosophila heparan sulfate 3-0 sulfotransferase B Null Mutant Is Viable and Exhibits No Defects in Notch Signaling

Heparan sulfate proteoglycans （HSPGs） are critically involved in a variety of biological events. The functions of HSPGs are determined by the nature of the core proteins and modifications of heparan sulfate （HS） glycosaminoglycan （GAG） chains. The distinct O-sulfo- transferases are important for nonrandom modifications at specific positions. Two HS 3-0 sulfotransferase （Hs3st） genes, Hs3st-A and Hs3st-B, were identified in Drosophila. Previous experiments using RNA interference （RNAi） suggested that Hs3st-B was required for Notch signaling. Here, we generated a null mutant of Hs3st-B via ends-out gene targeting and examined its role（s） in development. We found that homozygous Hs3st-B mutants have no neurogenic defects or alterations in the expression of Notch signaling target gene. Thus, our results strongly argue against an essential role for Hs3st-B in Notch signaling. Moreover, we have generated two independent Hs3st-A RNAi lines which worked to deplete Hs3st-A. Importantly, Hs3st-A RNAi combined with Hs3st-B mutant flies did not alter the expression of Notch signaling components, arguing that both Hs3st-A and Hs3st-B were not essential for Notch signaling. The establishment of Hs3st-B mutant and effective Hs3st-A RNAi lines provides essential tools for further studies of the physiological roles of Hs3st-A and Hs3st-B in development and homeostasis.

Propolis modulates vitronectin,laminin,and heparan sulfate/heparin expression during experimental burn healing

Objective:This study was aimed at assessing the dynamics of vitronectin (VN), laminin (LN), and heparan sulfate/heparin (HS/HP) content changes during experimental burn healing. Methods:VN, LN, and HS/HP were isolated and purified from normal and injured skin of domestic pigs, on the 3rd, 5th, 10th, 15th, and 21st days following thermal damage. The wounds were treated with apitherapeutic agent (propolis), silver sulfadiazine (SSD), physiological salt solution, and propolis vehicle. VN and LN were quantified using an immunoenzymatic assay and HS/HP was estimated by densitometric analysis. Results:Propolis treatment stimulated significant increases in VN, LN, and HS/HP contents during the initial phase of study, followed by a reduction in the estimated extracellular matrix molecules. Similar patterns, although less extreme, were observed after treatment with SSD. Conclusions:The beneficial effects of propolis on experimental wounds make it a potential apitherapeutic agent in topical burn management.

Collagen/heparan sulfate porous scaffolds loaded with neural stem cells improve neurological function in a rat model of traumatic brain injury

One reason for the poor therapeutic effects of stem cell transplantation in traumatic brain injury is that exogenous neural stem cells cannot effectively migrate to the local injury site,resulting in poor adhesion and proliferation of neural stem cells at the injured area.To enhance the targeted delivery of exogenous stem cells to the injury site,cell therapy combined with neural tissue engineering technology is expected to become a new strategy for treating traumatic brain injury.Collagen/heparan sulfate porous scaffolds,prepared using a freeze-drying method,have stable physical and chemical properties.These scaffolds also have good cell biocompatibility because of their high porosity,which is suitable for the proliferation and migration of neural stem cells.In the present study,collagen/heparan sulfate porous scaffolds loaded with neural stem cells were used to treat a rat model of traumatic brain injury,which was established using the controlled cortical impact method.At 2 months after the implantation of collagen/heparan sulfate porous scaffolds loaded with neural stem cells,there was significantly improved regeneration of neurons,nerve fibers,synapses,and myelin sheaths in the injured brain tissue.Furthermore,brain edema and cell apoptosis were significantly reduced,and rat motor and cognitive functions were markedly recovered.These findings suggest that the novel collagen/heparan sulfate porous scaffold loaded with neural stem cells can improve neurological function in a rat model of traumatic brain injury.This study was approved by the Institutional Ethics Committee of Characteristic Medical Center of Chinese People’s Armed Police Force,China(approval No.2017-0007.2)on February 10,2019.

Structural basis of heparan sulfate-specific degradation by heparinase Ⅲ

Heparinase Ⅲ(HepⅢ)is a 73-kDa polysaccharide lyase(PL)that degrades the heparan sulfate(HS)polysaccharides at sulfate-rare regions,which are important co-factors for a vast array of functional distinct proteins including the well-characterized antithrombin and the FGF/FGFR signal transduction system.It functions in cleaving metazoan heparan sulfate(HS)and providing carbon,nitrogen and sulfate sources for host microorganisms.It has long been used to deduce the structure of HS and heparin motifs;however,the structure of its own is unknown.Here we report the crystal structure of the HepⅢ from Bacteroides thetaiotaomicron at a resolution of 1.6Å.The overall architecture of HepⅢ belongs to the(α/α)5 toroid subclass with an N-terminal toroid-like domain and a C-terminal β-sandwich domain.Analysis of this high-resolution structure allows us to identify a potential HS substrate binding site in a tunnel between the two domains.A tetrasaccharide substrate bound model suggests an elimination mechanism in the HS degradation.Asn260 and His464 neutralize the carboxylic group,whereas Tyr314 serves both as a general base in C-5 proton abstraction,and a general acid in a proton donation to reconstitute the terminal hydroxyl group,respectively.The structure of HepⅢ and the proposed reaction model provide a molecular basis for its potential practical utilization and the mechanism of its eliminative degradation for HS polysaccarides.

非小细胞肺癌组织中CLDN10和CSPG4水平表达与临床病理特征及预后的关系研究

目的探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中紧密连接蛋白10(claudin 10,CLDN10)和硫酸软骨素蛋白聚糖4(chondroitin sulfate proteoglycan 4,CSPG4)表达与临床病理特征和预后的关系。方法随机选取2017年1月~2018年4月于南京医科大学附属泰州市人民医院进行手术的136例NSCLC患者为研究对象,并根据随访结局(生存或死亡)分为生存组(n=63)和死亡组(n=69)。收集136例患者于手术过程中切除的癌组织及癌旁组织标本;实时荧光定量PCR(real-time fluorescence quantitative PCR,RT-qPCR)检测癌组织及癌旁组织CLDN10和CSPG4表达水平,并分别以NSCLC患者癌组织中CLDN10和CSPG4表达水平的平均数为界限,分为CLDN10高表达组(n=66),CLDN10低表达组(n=70)和CSPG4高表达组(n=71),CSPG4低表达组(n=65);采用多因素COX回归分析确定NSCLC患者预后的影响因素;采用Kaplan-Meier生存曲线分析NSCLC患者CLDN10和CSPG4表达水平与其预后的关系。结果NSCLC组织中CLDN10表达水平(0.96±0.25)低于癌旁组织(1.73±0.42),CSPG4表达水平(1.80±0.46)高于癌旁组织(1.04±0.27),差异有统计学意义(t=18.372,16.617,均P<0.05)。与生存组比较,死亡组低未分化占比、淋巴结转移占比及癌组织中CSPG4表达水平较高,CLDN10表达水平较低,差异具有统计学意义(t/χ^(2)=8.463,7.423,11.696,6.426,均P<0.05)。CLDN10高表达组五年存活率(58.46%)高于低表达组(37.31%),CSPG4低表达组患者五年存活率(55.56%)高于高表达组(40.58%),差异有统计学意义(χ^(2)=7.848,4.018,均P<0.05)。多因素COX分析结果显示,CLDN10低表达、CSPG4高表达、低分化程度、淋巴结转移是NSCLC患者预后的危险因素(HR=1.362,1.368,1.335,1.314,均P<0.05)。结论NSCLC患者癌组织中CLDN10表达水平较低,CSPG4水平较高,且与NSCLC发展和预后密切相关。

Proteoglycans: Road Signs for Neurite Outgrowth

Proteoglycans in the central nervous system play integral roles as ＂traffic signals＂ for the direction of neurite outgrowth. This attribute of proteoglycans is a major factor in regeneration of the injured central nervous system. In this review, the structures of proteoglycans and the evidence suggesting their involvement in the response following spinal cord injury are presented. The review further describes the methods routinely used to determine the effect proteoglycans have on neurite outgrowth. The effects of proteoglycans on neurite outgrowth are not completely understood as there is disagreement on what component of the molecule is interacting with growing neurites and this ambiguity is chronicled in an historical context. Finally, the most recent findings suggesting possible receptors, interactions, and sulfation patterns that may be important in eliciting the effect of proteoglycans on neurite outgrowth are discussed. A greater understanding of the proteoglycan-neurite interaction is necessary for successfully promoting regeneration in the iniured central nervous system.

Traffic lights for axon growth: proteoglycans and their neuronal receptors

Axon growth is a central event in the development and post-injury plasticity of the nervous system. Growing axons encounter a wide variety of environmental instructions. Much like traffic lights in controlling the migrating axons, chondroitin sulfate proteoglycans （CSPGs） and heparan sulfate proteoglycans （HSPGs） often lead to ＂stop＂ and ＂go＂ growth responses in the axons, respectively. Recently, the LAR family and NgR family molecules were identified as neuronal receptors for CSPGs and HSPGs. These discoveries provided molecular tools for further study of mechanisms underlying axon growth regulation. More importantly, the identification of these proteoglycan receptors offered potential therapeutic targets for promoting post-injury axon regeneration.