Decorin基因与恶性肿瘤

Decorin是细胞基质组织中的一种富含亮氨酸小分子蛋白多糖,近年研究发现它在恶性肿瘤组织中异常表达,并在恶性肿瘤细胞生长过程中表现负性调控作用。本文综述了近年decorin基因在恶性肿瘤的表达、抗肿瘤作用及作用机制方面的研究。     

Decorin and biglycan retain LDL in disease-prone valvular and aortic subendothelial intimal matrix

Objective

Subendothelial LDL retention by intimal matrix proteoglycans is an initial step in atherosclerosis and calcific aortic valve disease. Herein, we identify decorin and biglycan as the proteoglycans that preferentially retain LDL in intimal matrix at disease-prone sites in normal valve and vessel wall.

Methods

The porcine aortic valve and renal artery ostial diverter, initiation sites of calcific valve disease and renal atherosclerosis, respectively, from normal non-diseased animals were used as models in these studies.

Results

Fluorescent human LDL was selectively retained on the lesion-prone collagen/proteoglycan-enriched aortic surface of the valve, where the elastic lamina is depleted, as previously observed in lesion-prone sites in the renal ostium. iTRAQ mass spectrometry of valve and diverter protein extracts identified decorin and biglycan as the major subendothelial intimal matrix proteoglycans electrostatically retained on human LDL affinity columns. Decorin levels correlated with LDL binding in lesion-prone sites in both tissues. Collagen binding to LDL was shown to be proteoglycan-mediated. All known basement membrane proteoglycans bound LDL suggesting they may modulate LDL uptake into the subendothelial matrix. The association of purified decorin with human LDL in an in vitro microassay was blocked by serum albumin and heparin suggesting anti-atherogenic roles for these proteins in vivo.

Conclusions

LDL electrostatic interactions with decorin and biglycan in the valve leaflets and vascular wall is a major source of LDL retention. The complementary electrostatic sites on LDL or these proteoglycans may provide a novel therapeutic target for preventing one of the earliest events in these cardiovascular diseases.     

Biochemical Changes of Extracellular Proteoglycans in Squamous Cell Laryngeal Carcinoma

Larynx is a complicated organ with peculiar properties, having a noticeable impact in vocal and respiratory physiology. In squamous cell laryngeal carcinoma, the extracellular matrix components underwent significant modifications concerning their fine chemical structure. Degradation of aggrecan is observed, whereas versican and decorin amounts are increased. The expression of aggrecan is almost totally ceased in later cancer stages, whereas decorin is expressed in normal and cancerous samples. But its expression is increased in cancer, being related to cancer stage. However, the expression of versican seems to be characteristic of the tumor, since none or traces expression is observed in normal samples. Chondroitin/dermatan sulfate is the major glycosaminoglycan, but its sulfation shows a shift from C6 position of galactosamine in normal samples to C4 in malignancy. Dermatan sulfate represents minor amounts in normal samples but increases in proportion up to one-fourth of total sulfated glycosaminoglycans in malignancy. In addition, an increase in the amounts of hyaluronan is also observed in malignant samples. Accumulated data demonstrate that tumor progression is closely related to the alteration of the expression and biochemical composition of specific extracellular constituents that describes the mild aggressive phenotype of squamous cell laryngeal carcinoma.     

Change in Decorin during Aging of Rat Placenta

By immunohistochemistry, with or without chondroitinases, decorin was found to be distributed in the extracellular matrix of chorionic villi and amnia. The strength of staining intensified with increasing gestational age. Decorin was isolated from the placenta of 13- to 20-day-old pregnant rats and identified by Western blotting, using an antidecorin core protein antibody. The molecular weight of decorin is ～100 kDa, whereas the respective figures for the core protein treated with chondroitinase (chase) ABC and with chase B are ～40 kDa and 43 kDa. The difference in the molecular weight between the core protein with chase ABC and B suggests that the glycosaminoglycan (GAG)- base structure on the core protein was chondroitin sulfate (CS) without dermatan sulfate (DS). The decorin content and the proportion of CS to DS in GAG increased with age. We concluded that the age-related changes in the GAG chain may be related to specific functional properties and may have a crucial role in placental tissue organization.     

Literature Review on the Clinical Relationship between Ulcerative Jejunoileitis,Coeliac Disease,and Enteropathy-associated T-Cell Lymphoma

Background: The small interstitial proteoglycans decorin and biglycan have been shown to interact with various extracellular matrix molecules and with transforming growth factor-β. These interactions are proposed to be important for tissue repair, as the former interactions may affect the diameter and spacing of collagen fibrils, and the latter interaction the proliferation and differentiation of cells embedded in the matrix. The aim of this study is to localize these proteoglycans in the stomach and to investigate their suitability as potential markers of extracellular matrix activity in gastric lesions. Methods: Immunohis-tochemical techniques and in situ hybridization were used to study the phenotypic expression of these two proteoglycans in routinely processed specimens of human stomach tissue from 8 patients with gastric ulcer and 10 healthy control persons. Results: In normal gastric tissue, immunostaining for both proteoglycans was found in the interstitium, with a more pronounced staining in the pylorus region than in the corpus area. In addition, biglycan showed a strong staining of parietal cells. In specimens of healing gastric ulcers a larger deposition of decorin throughout scar tissue could be shown, and a higher expression of decorin was also found by in situ hybridization. Biglycan was only found at the edges of the lesions. Conclusion: This study shows for the first time the presence of decorin and biglycan in human gastric mucosa. We also showed that these proteoglycans may be involved in the gastric ulcer healing processes.     

核心蛋白聚糖抑制兔屈趾肌腱术后粘连的实验研究

目的探讨核心蛋白聚糖(decorin,DCN)抑制兔屈趾肌腱术后粘连的效果.方法日本大耳白兔18只,其后肢第2趾供实验用,将伸屈趾肌腱横断,作改良的Kessler缝合,不缝合腱鞘,右侧腱鞘内肌腱缝合位点直接注射DCN 100 μl (0.25 mg/ml)作为实验趾;左侧直接注射PBS 100 μl作对照趾.术后2、4及8周取材,行大体观察、生物力学检测和组织学观察.结果大体观察,术后各时间点实验趾的粘连程度明显小于对照趾.生物力学检测显示各时间点实验趾肌腱滑移距离和关节总屈曲度明显大于对照趾,差异有统计学意义(P＜0.05).组织学观察见实验趾术后2周成纤维细胞增生不明显,4周增生明显,8周胶原纤维排列规则,直径大小均一;对照趾2周成纤维细胞增生,4周成纤维细胞增生减少,8周胶原纤维排列不规则,直径大小不一.结论核心蛋白聚糖能明显减少屈趾肌腱损伤的术后粘连,调节胶原纤维的形成,促进肌腱愈合.     

鼠肌核心蛋白聚糖的研制

目的 :从动物组织中提取纯化核心蛋白聚糖 (Decorin) ,检测其活性。方法 :以大鼠肌肉为原料 ,采用匀浆、透析、层析等步骤分离、纯化Decorin ,经SDS PAGE检测其分子量和纯度 ,并经细胞株A5 49检测生物学活性结果 :Decorin在SDS PAGE显示分子量约为 37～ 38kD两条带 ,得率约为 2mg/g组织 ,对A5 49具有明显的抑制生长活性 ,抑制率 >5 0 %。结论 :此法获得的Decorin将有可能作为天然药物用于治疗肿瘤。     

重组核心蛋白多糖对人正常皮肤和增生性瘢痕成纤维细胞增及生物学活性的影响

目的　观察重组核心蛋白多糖 (Decorin)对人正常皮肤和增生性瘢痕成纤维细胞体外增殖和生物学活性的影响 ,以探讨Decorin在增生性瘢痕形成和成熟中的作用。　方法　分离培养人正常皮肤和增生性瘢痕成纤维细胞 ,分别加入不同质量浓度 (0 .0 1,0 .1,2 ,10 μg/ml)的重组Decorin ;培养 12 ,2 4 ,4 8h用二甲基噻唑二苯基四唑溴盐 (MTT)法测定细胞增殖速度 ;培养 4 8h用流式细胞仪检测细胞周期和凋亡 ;收集细胞培养上清 ,ELISA法检测TGF - β1蛋白水平 ,放射免疫方法检测Ⅰ、Ⅲ型前胶原蛋白 (PCⅠ、PCⅢ )含量。　结果　 2 ,10 μg/ml的Decorin可有效抑制正常皮肤和增生性瘢痕成纤维细胞的增殖 (P <0 .0 5或P <0 .0 1) ,明显增加两种细胞处于G1期的百分比(P <0 .0 1) ;并抑制细胞分泌转化生长因子 (TGF) - β1和PCⅠ、PCⅢ ,下调PCⅠ /PCⅢ比值。实验组和对照组 (未加重组Decorin)均未检测到终末期凋亡细胞。　结论　Decorin可抑制正常皮肤和增生性瘢痕成纤维细胞的增殖及其生物学活性 ,可能在预防增生性瘢痕形成和促进瘢痕成熟中起一定的作用。     

采用消减杂交初步筛选先兆子痫病理相关基因

目的 应用抑制性消减杂交、PCR技术，克隆出与先兆子痫有关的高表达基因和(或)新基因。方法 分别从正常妊娠分娩胎盘和先兆子痫患者分娩胎盘中提取mRNA，采用抑制性消减杂交、PCR技术，构建先兆子痫胎盘cDNA文库，采用反向杂交验证，测序分析；以初步筛选的差异表达基因为探针，与先兆子痫和正常胎盘总体mRNA斑点杂交。结果 构建成功具有高消减效率的与先兆子痫相关cDNA消减文库，文库扩增后得到60个阳性克隆，经杂交验证，有34个阳性克隆有插入片断，随机挑取一阳性克隆菌落，测序分析发现该差异表达基因为核蛋白多糖基因，以该差异表达基因为探针，与先兆子痫和正常胎盘总体mRNA斑点杂交，观察其在总体胎盘中的表达。结论 人类先兆子痫胎盘基因表达同正常胎盘相比，核蛋白多糖呈差异表达基因，该基因差异表达可能与先兆子痫的发病有关．