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Collagen Type IV (collagen + type_iv)

Distribution by Scientific Domains

Medical Sciences	64%

Selected Abstracts

Synthesis of heterotrimeric collagen peptides containing the ,1,1 integrin recognition site of collagen type IV

JOURNAL OF PEPTIDE SCIENCE, Issue 5 2002
Barbara Saccá
Abstract Collagen type IV provides a biomechanically stable scaffold into which the other constituents of basement membranes are incorporated, but it also plays an important role in cell adhesion. This occurs with collagen type IV mainly via the ,1,1 integrin, and the proposed epitope involved in this type of collagen/integrin interaction corresponds to a non-sequential R/Xaa/D motif, where the arginine and aspartate residues are provided by the ,2 and ,1 chains of the collagen molecule, respectively. Since the stagger of the three , chains in native collagen type IV is still unknown and different alignments of the chains lead to different spatial epitopes, two heterotrimeric collagen peptides containing the natural 457,469 sequences of the cell adhesion site were synthesized in which the single chains were assembled via disulfide bonds into the two most plausible ,1,2,1, and ,2,1,1, registers. The differentiated triple-helical stabilities of the two heterotrimers suggest a significant structural role of the chain register in collagen, although the binding to ,1,1 integrin is apparently less affected as indicated by preliminary experiments. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd. [source]

A clinicopathological study of the expression of extracellular matrix components in urothelial carcinoma

BJU INTERNATIONAL, Issue 4 2005
Elli Ioachim
OBJECTIVE To measure the immunohistochemical expression of the extracellular matrix (ECM) components tenascin, fibronectin, collagen type IV and laminin in urothelial carcinomas, and to correlate their expression with clinicopathological features to clarify the prognostic value of these molecules and their role in tumour progression. MATERIALS AND METHODS Tumour specimens obtained during transurethral resection of bladder tumour (TURBT) from 103 patients (82 men and 2 1 women, mean age 66.7 years, range 27,89) were studied retrospectively. The expression of tenascin, fibronectin, collagen type IV and laminin was correlated with clinicopathological features (tumour grade and stage, multiplicity, simultaneous in situ component, the proliferative activity as estimated by the two proliferation associated indices, Ki-67 and proliferating cell nuclear antigen, the recurrence rate, and the progression of invading tumour). Specimens investigated for tenascin expression from patients with superficial bladder cancers were categorized into 28 treated by TURBT only and 53 who had TURBT followed by intravesical instillations of interferon. RESULTS Cytoplasmic tenascin expression was detected in tumour cells in 20% of specimens. Tenascin was expressed in the tumour stroma in 76% of specimens, and was positively correlated with tumour grade and stage. Stromal tenascin expression was positively correlated with proliferative activity, and with the expression of fibronectin and collagen type IV. Fibronectin was expressed in the tumour stroma in 89% of specimens and was positively correlated with tumour stage, proliferative activity, and expression of collagen type IV and laminin. Collagen type IV was expressed in 93% of specimens, and was positively correlated with tumour grade and stage. Laminin was expressed in 78% of specimens and had no significant correlation with the clinicopathological features. Patients treated with TURBT alone and who had low levels of tenascin had a longer tumour-free interval than those with high levels of tenascin. CONCLUSION Levels of tenascin might be valuable for predicting the risk of early recurrence. The expression of tenascin, fibronectin and collagen type IV seems to be correlated with more aggressive tumour behaviour. Furthermore, their interrelationships could indicate that they are involved in the remodelling of bladder cancer tissue, probably influencing tumour progression. [source]

Vero Cell Growth and Differentiation on Poly(l -Lactic Acid) Membranes of Different Pore Diameters

ARTIFICIAL ORGANS, Issue 1 2001
Arnaldo R. Santos Jr.
Abstract: In the last few years, the demand has increased for research on polymeric materials, which can be used as substitutes for injured tissues and organs or to improve their regeneration. In this work, we studied poly(l -lactic acid) (PLLA) membranes, a resorbable biomaterial, which were either dense or had different pore diameters (less than 45 ,m, between 180 and 250 ,m, and between 250 and 350 ,m), in relation to stimulation of cell adhesion, growth, and differentiation in vitro. We used Vero cells, a fibroblastic cell line, as the biological model of investigation. We found that cells attached slowly to all PLLA membranes studied. On the other hand, once the adhesion occurs, the cells are able to grow and differentiate on the different polymers. The cells grew to form a confluent monolayer and were capable of producing collagen Type IV and fibronectin on different PLLA membranes. This behavior indicates that cells try to create a better environment to stimulate their growth. This also indicates that Vero cells alter their differentiation pattern once they are producing extracellular matrix molecules related to epithelial differentiation. [source]

From collagen chemistry towards cell therapy , a personal journey

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2007
Michael E. Grant
Summary The Fell,Muir Award requires the recipient to deliver a lecture and a review manuscript which provides a personal overview of significant scientific developments in the field of matrix biology over the period of the recipient's career. In this context, this review considers the collagen family of structural proteins and the advances in biochemical, molecular biological and genetic techniques which led to the elucidation of the structure, synthesis and function of this important group of extracellular matrix constituents. Particular attention is focussed on early research on the identification and assembly of the soluble precursors of collagen types I and II, and the identification of the precursor of basement membrane collagen type IV. In subsequent studies investigating the maintenance of the chick chondrocyte phenotype in culture, the influence of the extracellular milieu was found to influence markedly both cell morphology and collagen gene expression. These studies led to the discovery of collagen type X whose expression is restricted to hypertrophic chondrocytes at sites of endochondral ossification. Such research provided a prelude to investigations of mammalian endochondral ossification which is known to be aberrant in a variety of human chondrodysplasias and is reactivated in bone fracture repair and in osteoarthritis. The cloning of bovine and then human collagen type X genes facilitated studies in relevant human diseases and contributed to the discovery of mutations in the COL10A1 gene in families with metaphyseal chondrodysplasia type Schmid. Clustering of mutations in the C-terminal domain of the type X collagen molecule has now been widely documented and investigations of the pathogenic mechanisms in animal models are beginning to suggest the prospect of novel treatment strategies. [source]

Decorin transfection in human mesangial cells downregulates genes playing a role in the progression of fibrosis

JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 4 2002
Antonia Costacurta
Abstract The proteoglycan decorin inhibits TGF-,; therefore, it could antagonize progression of fibrotic diseases associated with activation of TGF-,1. The effect of decorin transfection in human mesangial cells (HMCs) on the expression of genes related to kidney fibrosis was investigated. HMCs, isolated from glomeruli of healthy portions of human kidneys removed due to carcinoma, were histochemically typed. Decorin cDNA cloned in a eukaryotic expression vector was transfected into HMCs. Gene expression of fibrogenetic cytokines and fibrotic proteins TGF-,1, PDGF-,, ,1 collagen type IV, ,1 collagen type I, fibronectin, and tenascin was analyzed, by reverse transcription polymerase chain reaction (RT-PCR), 24 hr after transfection. Immunoblotting analysis of protein extracts using anti-decorin IgG, revealed a positive signal of about 52 MDa, corresponding to the molecular weight of decorin, in cultures transfected with the decorin gene. Decorin mRNA increased about 12 times in cultures transfected with the construct pCR3.1-Deco. Cells with increased decorin synthesis showed a 61% decrease of TGF-,1 mRNA, a 71% reduction of ,1 collagen type IV mRNA, and a 29% reduction of fibronectin mRNA. This study is the first to investigate decorin transfection into human mesangial cells, and supports the use of the decorin gene to control the progression of glomerular and interstitial fibrosis in kidney diseases. © 2002 Wiley-Liss, Inc. [source]

Proliferation and differentation markers in snuff-induced oral mucosal lesions

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 5 2002
Marina Merne
Abstract Background: Regular use of snuff is known to cause whitish oral mucosal lesions of variable severity at the usual quid placement site. The main aim of this study was to elucidate cellular mechanisms involved in snuff-induced epithelial changes. Methods: Expression patterns for markers of cell proliferation (PCNA, Ki-67), cell cycle regulation (p53, p21), keratin changes (pankeratin, CK18, CK19), cell stress (HSP 70) and collagen type IV in 14 snuff-induced oral mucosal lesions and 12 control samples were analyzed by immunohistochemistry (IHC). Results: On light microscopy, all snuff-induced lesions were characterized by a hyperkeratinized and thickened epithelium. Some vacuolized cells, markers of cell degeneration, were frequently seen (in 9/14 of the samples) in the superficial layers in epithelia. Expression of PCNA and Ki-67 was found in a statistically significantly fewer cells in snuff-induced lesions (P < 0.001) than in the controls. This indicates that epithelia in snuff-induced lesions are not thickened as a result of increased cellular proliferation, but by protracted turnover of differentiating cells. Of cell cycle markers, p21 was found be up-regulated in 4/14 snuff-induced lesions, probably by p53-independent pathways. Only two snuff-induced lesions showed p53 positivity. However, the number of stained cells with p53 and p21 was not statistically different from that in controls. Expression of CK18, but not any alterations in CK19 expression, was seen in 5 of 14 snuff-induced lesions. Snuff also seems to stimulate the expression of collagen type IV, possibly by basal cells, as indicated by the thickened staining of the basal lamina. Conclusions: The findings of this study showing suppressed cellular proliferation and infrequent p53 dysfunction in snuff lesions may partly explain why dysplastic changes are seldom seen in mucosal lesions induced by the Scandinavian type of snuff. [source]

Synthesis of heterotrimeric collagen peptides containing the ,1,1 integrin recognition site of collagen type IV

Remodeling of extracellular matrix at ovulation of the bovine ovarian follicle

MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 10 2006
H.F. Irving-Rodgers
Abstract Using immunohistochemistry and RNA analyses we examined the fate of components of a newly identified matrix that develops between granulosa cells (focimatrix, abbreviated from focal intraepithelial matrix) and of the follicular basal lamina in ovulating bovine ovarian follicles. Pre- and postovulatory follicles were generated by treatment with estradiol (Day 1), progesterone (Days 1,10), and prostaglandin analogue (Day 9) with either no further treatment (Group 1, n,=,6) and or with 25 mg porcine LH (Day 11, Group 2, n,=,8 or Day 10, Group 3, n,=,8) and ovariectomy on Day 12 (12,14 hr post LH in Group 2, 38,40.5 hr in Group 3). In the time frame examined no loss of follicular basal lamina laminin chains ,2 and ,1 or nidogen 1 was observed. In the follicular basal lamina collagen type IV ,1 and perlecan were present prior to ovulation; after ovulation collagen type IV ,1 was discontinuously distributed and perlecan was absent. Versican in the theca interna adjacent to the follicular basal lamina in preovulatory follicles was not observed post ovulation, however, the granulosa cells then showed strong cytoplasmic staining for versican. Expression of versican isoforms V0, V1, and V3 was detected at all stages. Focimatrix was observed in preovulatory follicles. It contained collagen type IV ,1, laminins ,2 and ,1, nidogen 1 and perlecan and underwent changes in composition similar to that of the follicular basal lamina. In conclusion focimatrix and the follicular basal lamina are degraded at ovulation. Individual components are lost at different times. Mol. Reprod. Dev. © 2006 Wiley-Liss, Inc. [source]

Expression of basement membrane components in odontogenic cysts

ORAL DISEASES, Issue 3 2006
S Poomsawat
Objective:, To compare the expression of basement membrane components (BMCs), including laminins 1 and 5, collagen type IV, and fibronectin in odontogenic keratocysts (OKCs) with dentigerous cysts (DCs) and radicular cysts (RCs). Materials and methods:, Basement membrane components were analysed in 20 OKCs, 20 DCs and 20 RCs using an immunohistochemical technique. Results:, Odontogenic keratocysts, DCs and RCs showed positive reaction to all BMCs studied, with different distributions and intensity. OKCs showed continuous linear deposits for laminins 1 and 5 but two staining patterns (continuous and discontinuous) for collagen type IV and fibronectin. DCs exhibited continuous linear deposits for laminins 1 and 5 and collagen type IV but a discontinuous linear deposit for fibronectin. RCs displayed similar results to DCs for laminin 1, collagen type IV and fibronectin. Laminin 5 in RCs had two staining patterns. Constant results in all cysts were strong intensity for laminin 1 and moderate intensity for laminin 5. Conclusions:, Substantial differences in the expression of BMCs among studied cysts were not observed, suggesting that the separation of the epithelial lining in OKCs is not associated with the existence of these proteins. [source]

Mangiferin prevents diabetic nephropathy progression in streptozotocin-induced diabetic rats

PHYTOTHERAPY RESEARCH, Issue 6 2010
Xuan Li
Abstract Diabetic nephropathy is one of the most severe diabetic microangiopathies and accounting for approximately one-third of all cases of end-stage renal disease. In the present study, we investigated the effect of mangiferin, a polyphenol from Anemarrhena asphodeloides Bge. or Mangifera indica L., on diabetic nephropathy and the possible mechanisms by using a developed diabetic nephropathy rat model and cultured rat mesangial cells. Serum-advanced glycation end-products level, malonaldehyde level, sorbitol concentration of red blood cell, 24,h albuminuria excretion were significantly decreased, whereas activity of serum superoxide dismutase and glutathione peroxidase and creatinine clearance rate were increased by mangiferin. Blood glucose level remained unaffected. Mangiferin significantly inhibited glomerular extracellular matrix expansion and accumulation and transforming growth factor-beta 1 overexpression in glomeruli of diabetic nephropathy rats. Moreover, mangiferin was observed to inhibit proliferation of mesangial cells induced by high glucose and the overexpression of collagen type IV of mesangial cells induced by advanced glycation end products. In summary, mangiferin could significantly prevent progression of diabetic nephropathy and improve renal function. Copyright © 2009 John Wiley & Sons, Ltd. [source]

A clinicopathological study of the expression of extracellular matrix components in urothelial carcinoma

Low-energy helium,neon laser induces melanocyte proliferation via interaction with type IV collagen: visible light as a therapeutic option for vitiligo

BRITISH JOURNAL OF DERMATOLOGY, Issue 2 2009
C-C.E. Lan
Summary Background, The treatment of vitiligo remains a challenge for clinical dermatologists. We have previously shown that the helium,neon laser (He,Ne laser, 632·8 nm) is a therapeutic option for treatment of this depigmentary disorder. Objectives, Addressing the intricate interactions between melanocytes, the most important cellular component in the repigmentation scheme of vitiligo, and their innate extracellular matrix collagen type IV, the current study aimed to elucidate the effects of the He,Ne laser on melanocytes. Methods, Cultured melanocytes were irradiated with the He,Ne laser. Relevant biological parameters including cell attachment, locomotion and growth were evaluated. In addition, the potentially involved molecular pathways were also determined. Results, Our results show that in addition to suppressing mobility but increasing attachment to type IV collagen, the He,Ne laser stimulates melanocyte proliferation through enhanced ,2,1 integrin expression. The expression of phosphorylated cyclic-AMP response element binding protein (CREB), an important regulator of melanocyte growth, was also upregulated by He,Ne laser treatment. Using a specific mitochondrial uncoupling agent [carbonyl cyanide m-chlorophenyl-hydrazone (CCCP)], the proliferative effect of the He,Ne laser on melanocytes was abolished and suppression of melanocyte growth was noted. Conclusions, In summary, we have demonstrated that the He,Ne laser imparts a growth stimulatory effect on functional melanocytes via mitochondria-related pathways and proposed that other minor pathways including DNA damage may also be inflicted by laser treatment on irradiated cells. More importantly, we have completed the repigmentation scheme of vitiligo brought about by He,Ne laser light in vitro and provided a solid theoretical basis regarding how the He,Ne laser induces recovery of vitiligo in vivo. [source]

Increased expression of collagen receptors: ,1,1 and ,2,1 integrins on blood eosinophils in bronchial asthma

CLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2006
S. Bazan-Socha
Summary Background Eosinophils are one of the major effector cells in bronchial asthma. Their infiltration of airways correlates with the asthma severity. Recruitment and activation of eosinophils are partially mediated by integrins ,4,1 and ,4,7. Collagens type I and IV constitute important components of extracellular matrix and vascular basement membrane, respectively. Therefore, collagen-binding integrins (,1,1 and ,2,1) may also play a role in eosinophil lung infiltration. Objective To evaluate the possible presence of ,1,1 and ,2,1 integrins on peripheral blood eosinophils from asthmatic subjects. Methods Collagen receptors were studied on eosinophils separated by immunomagnetic CD16-negative method from healthy donors (n=13) and patients with moderate persistent atopic bronchial asthma (n=15). Surface receptor identification was performed by flow cytometry and cell adhesion assay. Results Eosinophils isolated from the patients showed increased expression of both ,1,1 and ,2,1 integrins as compared with healthy controls. Moreover, adhesive function of eosinophils to collagen type IV was inhibited by snake venom disintegrins: viperistatin and obtustatin. These disintegrins contain KTS active motif and are specific inhibitors of ,1,1 integrin. Conclusion We demonstrated for the first time that collagen receptors: ,1,1 and ,2,1 integrins are overexpressed on the surface of peripheral blood eosinophils of asthmatic subjects. Further studies may reveal potential application of KTS-disintegrins or their structural analogs for therapy of bronchial asthma. [source]

Living related kidney transplantation in a patient with autosomal-recessive Alport syndrome

CLINICAL TRANSPLANTATION, Issue 2003
Ken Sakai
Abstract:, We discuss a patient with Alport syndrome who received a renal transplant from a donor with thin basement membrane disease. A 30-year-old woman, diagnosed with Alport syndrome on the basis of sensorineural hearing loss, characteristic renal biopsy findings and a family history of microhaematuria, entered chronic haemodialysis therapy. She then received a renal transplant donated from her father, who had sensorineural hearing loss and persistent microhaematuria. On the day of renal transplantation, a 1-h graft biopsy after reperfusion showed thin basement membrane disease. We re-tested the patient's native kidney biopsy specimen by immunohistochemical staining using ,-chain-specific collagen type IV monoclonal antibodies. There was no expression of collagen type IV ,3-, ,4- and ,5-chain on glomerular basement membrane, but positive staining of ,5-chain on Bowman's capsular basement membrane was noted. A diagnosis of autosomal-recessive Alport syndrome was made. We concluded that this family might display different phenotypic expressions of the same genotype: one suffered end-stage renal disease and the other thin basement membrane disease. [source]