核心蛋白聚糖在特发性肺纤维化患者血清中的表达及其意义

[目的]探讨核心蛋白聚糖(DCN)在特发性肺纤维化(IPF)患者血清中的表达及其意义.[方法]选取2016年3月至2018年3月在陕西省第四人民医院诊治的87例IPF患者(IPF组)、82例特发性间质性肺炎(idiopathic interstitial pneumonia,IIP)患者(非IPF组)和100例健康体检...     

Altered distribution of urinary glycosaminoglycans in diabetic subjects

We studied the influence of type 1 and type 2 diabetes mellitus with similar duration on the urinary excretion of total glycosaminoglycans and alteration of urinary glycosaminoglycan distribution pattern. Investigations were performed in the 24-hour urine samples of 31 children with type 1 diabetes mellitus, 36 adults with type 2 diabetes mellitus and in 30 age-matched controls for each group. We found that type 2 diabetes mellitus also induced an increased urinary excretion of total glycosaminoglycans and that both type 1 and type 2 diabetes alter the urinary distribution of heparan sulphate and dermatan sulphate. Observed changes correlate with duration of the disease. Microalbuminuria was detected in 9 of 36 type 2 adult diabetics (25%). The microalbuminic group had a significanlty higher heparan sulphate and/or dermatan sulphate excretion rate. To clarify whether an altered urinary distribution of heparan sulphate and dermatan sulphate may precede the development of microalbuminuria, it is necessary to performed a prospective study in which urinary glycosaminoglycans and microalbuminuria are measured year by year starting from the diagnosis of diabetes. Received: 23 August 2001 / Accepted in revised form: 3 April 2002     

Proteoglycan mediated lipoprotein retention: A mechanism of diabetic atherosclerosis

The response to retention hypothesis outlines the initial stages of atherosclerotic lesion formation. The central theme of the hypothesis is that proteoglycan mediated lipoprotein retention plays a critical step in the initiation of atherosclerosis development. Recent research using human arterial specimens, transgenic mouse models and molecular biology techniques have added to our understanding of atherosclerosis development, and provided experimental data in support of the response to retention hypothesis. In this review we summarize the recent data, in particular that which addresses mechanisms by which diabetes can accelerate atherosclerosis formation, with a focus on proteoglycan-mediated LDL retention.     

Modulation of Rat Intestinal Nuclear Factor NF-κB by Gum Arabic

The objective of this study was to test the hypothesis that in an animal model of cathartic-induce intestinal dysfunction the proabsorptive effects of gum arabic (GA) could be associated with modulation of nuclear factor-κB (NF-κB) and with reduction of the inflammatory response caused by cathartics, as evidenced by intestinal mucosa cytokine production and gene expression. Juvenile male rats were given a phenolphthalein–magnesium citrate solution for 6 days, by itself or supplemented with either 10 or 20 g L⁻¹ GA, as a sole source of fluid. The controls given were tap water alone or with added 20 g L⁻¹ GA. The animals were euthanized and small-intestinal mucosa nuclear fractions and RNA were isolated. NF-κB p65 activity was highest after administration of cathartics, lowest in controls, and intermediate in GA-treated rats. Mucosal IL-1β was overexpressed in tissues from cathartic-treated rats and from rats given high-GA solutions. Gene-array analysis revealed a complex pattern of gene regulation by cathartics which selectively upregulated several subfamilies of cytochrome P-450 family 2 genes. Co-administration of GA did not block this effect. These findings suggest that local anti-inflammatory effects on the small intestine could be obtained by administration of a nonabsorbable proteoglycan such as GA. Supported in part by a grant of The Feinstein Institute for Medical Research     

Regulation of pancreatic endocrine cell differentiation by sulphated proteoglycans

Aims/hypothesis Epithelium–mesenchyme interactions play a major role in pancreas development. Recently, we demonstrated that embryonic pancreatic mesenchyme enhanced progenitor cell proliferation but inhibited endocrine cell differentiation. Here, we investigated the role played by sulphated proteoglycans, which are known to be essential to embryonic development, in this inhibitory effect. Materials and methods We first determined the expression of the genes encoding glypicans, syndecans and the main glycosaminoglycan chain-modifying enzymes in immature embryonic day (E) 13.5 and more differentiated E17.5 rat pancreases. Next, using an in vitro model of pancreas development, we blocked the action of endogenous sulphated proteoglycans by treating embryonic pancreases in culture with chlorate, an inhibitor of proteoglycan sulphation, and examined the effects on pancreatic endocrine cell differentiation. Results We first showed that expression of the genes encoding glypicans 1, 2, 3 and 5 and heparan sulphate 2-sulfotransferase decreased between E13.5 and E17.5. We next found that alteration of proteoglycan action by chlorate blocked the inhibitory effect of the mesenchyme on endocrine differentiation. Chlorate-treated pancreases exhibited a dramatic increase in beta cell number in a dose-dependent manner (169-and 375-fold increase with 30 mmol/l and 40 mmol/l chlorate, respectively) and in alpha cell development. Insulin-positive cells that developed in the presence of chlorate exhibited a phenotype of mature cells with regard to the expression of the following genes: pancreatic and duodenal homeobox gene 1 (Pdx1), proprotein convertase subtilisin/kexin type 1 (Pcsk1; previously known as pro-hormone convertase 1/3), proprotein convertase subtilisin/kexin type 2 (Pcsk2; previously known as pro-hormone convertase 2) and solute carrier family 2 (facilitated glucose transporter), member 2 (Slc2a1; previously known as glucose transporter 2). Finally, we showed that chlorate activated endocrine cell development by inducing neurogenin 3 (Neurog3) expression in early endocrine progenitor cells. Conclusions/interpretation We demonstrated that sulphated proteoglycans control pancreatic endocrine cell differentiation. Understanding the mechanism by which sulphated proteoglycans affect beta cell development could be useful in the generation of beta cells from embryonic stem cells. Electronic supplementary material The online version of this article () contains supplementary material, which is available to authorised users.     

Characterization of the macromolecular components of the articular cartilage surface

The intact surface of articular cartilage is a highly organized structure composed of a variety of macromolecules. The studies reported here deal with a partial characterization of the non-covalently bound components of the outermost layer of articular cartilage. Normal bovine and human cartilage articular surfaces were extracted for 5 min with 4-M guanidine HCl solution. Analysis and quantitation of small proteoglycans in the extract were carried out by PAGE (polyacrylamide gel electrophoresis), Western blot, and radioimmunoassays. The present studies indicate that the major proteins extracted from the articular surface of bovine and human cartilage are the collagen-binding small proteoglycans designated as fibromodulin and albumin. Fibronectin, decorin, and biglycan were also detected in smaller amounts. Immunoblotting of the surface material developed with a monoclonal antibody with keratan sulfate specificity confirmed the presence of fibromodulin coinciding with the major protein band of approximately 70–100-kDa molecular mass. Gel filtration chromatography of the surface material confirmed the previous results. Additional in vitro assays showed that the collagen-binding material extracted from the cartilage surface contained the small proteoglycans. Anti-human fibromodulin antibodies bound in significantly greater amounts to the intact articular surfaces than to cut surfaces of normal human cartilage. It is concluded that small, non-aggregating proteoglycans constitute the major proteoglycan species non-covalently bound to macromolecules at the articular surface of cartilage partially responsible for the interference of anti-collagen type II antibody binding and for the inhibition of cell adhesion to the intact surface. Received: 3 May 1998 / Accepted: 5 June 1998