scholarly journals Type IV collagen immunoreactivity of basement membrane in inflammatory-regenerative and dysplastic lesions of the flat colonic mucosa

2003 ◽  
Vol 3 (1) ◽  
pp. 30-35
Author(s):  
Svjetlana Radović ◽  
Ivan Selak ◽  
Mirsad Babić ◽  
Željka Knežević ◽  
Zora Vukobrat-Bijedić
Keyword(s):  
Basement Membrane ◽  
Colon Adenocarcinoma ◽  
Normal Mucosa ◽  
Collagen Iv ◽  
Epithelial Dysplasia ◽  
Collagen Type Iv ◽  
Severe Dysplasia ◽  
Colon Mucosa ◽  
Mild Dysplasia ◽  
Type Iv

The aim of this research is to establish by immunohistochemistry if there is a change in the expression of collagen type IV, as a substitute of basement membrane, in development of epithelial dysplasia in chronically inflamed colon mucosa.Methods. Biopsy specimens from 270 patients were examined: 74 were classified as inflammatory-regenerative and 196 as dysplastic lesions. There were 108 cases of mild dysplasia, 58 cases of moderate and 30 cases severe dysplasia, respectively. Visualisation of collagen IV and its way of expression within basement membrane of glandular crypts was performed by immunohistochemistry and then compared with findings in normal colon mucosa and colon adenocarcinoma tissue.Results. Changes in the expression of collagen IV comprised of its focal irregularities, diffuse thinning and/or thickening, focal interruptions or its complete absence. Significant changes in the expression of collagen IV in relation to normal mucosa already occur in inflammatory-regenerative mucosa. In mild dysplasia, these changes are more intensive in relation to those in inflammatory altered mucosa as well as at severe dysplasia in relation to moderate dysplasia. Changes in the expression of collagen IV in severe dysplasia are significantly more serious than in moderate dysplasia but are identical to those in colon adenocarcinoma tissue.Conclusion. These findings suggest that change in the expression of collagen IV is in correlation to a degree of epithelial dysplasia that developed in flat chronically inflamed colon mucosa.

scholarly journals Collagen IV and laminin expression in squamous cell carcinomas of lower lip and tongue

2016 ◽  
Vol 19 (2) ◽  
pp. 82
Author(s):  
João Luiz de Miranda ◽  
Dhelfeson Willya Douglas de Oliveira ◽  
Rafael Menezes-Silva ◽  
Roseana De Almeida Freitas
Keyword(s):  
Basement Membrane ◽  
Squamous Cell ◽  
Immunohistochemical Analysis ◽  
Collagen Iv ◽  
Squamous Cell Carcinomas ◽  
Matrix Proteins ◽  
Biological Behavior ◽  
Collagen Type Iv ◽  
Lower Lip ◽  
Type Iv

<p class="western" align="justify"><span style="font-family: Arial, serif;"><span><span lang="en-US"><strong>O</strong></span></span></span><span style="font-family: Arial, serif;"><span><span lang="en-US"><strong>bjective: </strong></span></span></span><span style="font-family: Arial, serif;"><span><span lang="en-US">In this study, the expression of the extracellular matrix proteins was immunohistochemically studied and compared with the histological grading of squamous cell carcinomas of the lower lip and tongue. </span></span></span><span style="font-family: Arial, serif;"><span><span lang="en-US"><strong>Material and M</strong></span></span></span><span style="font-family: Arial, serif;"><span><span lang="en-US"><strong>ethods: </strong></span></span></span><span style="font-family: Arial, serif;"><span><span lang="en-US">The lower lip carcinomas (n=12) and the tongue carcinomas (n=12) were histopathologically graduated according to Bryne’s method. The immunohistochemical technique utilized specific antibodies to collagen IV and laminin. Histopathologic and immunohistochemical analysis were carried-out on the tumoral invasive front. </span></span></span><span style="font-family: Arial, serif;"><span><span lang="en-US"><strong>R</strong></span></span></span><span style="font-family: Arial, serif;"><span><span lang="en-US"><strong>esults: </strong></span></span></span><span style="font-family: Arial, serif;"><span><span lang="en-US">Most of lower lip carcinomas (91.7%) was classified in lower score and all tongue carcinomas (100%) in high score malignant grade (p&lt;0.01). Collagen type IV expression was absent in the peritumoral basement membrane in 50% of lower lip carcinomas and in 66.7% of tongue carcinomas (p=0.09). Laminin expression was absent in the peritumoral basement membrane in 66.7% of lower lip carcinomas and in 58.3% of tongue carcinomas (p=0.48). When these two glicoproteins were expressed, they showed a linear, thin and discontinuous pattern and a weak intensity of expression. </span></span></span><span style="font-family: Arial, serif;"><span><span lang="en-US"><strong>C</strong></span></span></span><span style="font-family: Arial, serif;"><span><span lang="en-US"><strong>onclusion: </strong></span></span></span><span style="font-family: Arial, serif;"><span><span lang="en-US">The high score malignancy grade of the tongue carcinomas associated with the expression pattern of the studied matrix proteins. It suggests that tongue squamous cell carcinomas have more invasive potential and more aggressive biological behavior than the lower lip carcinomas.</span></span></span></p><p class="western" lang="en-US" align="justify"> </p><p class="western" align="justify"><span style="font-family: Arial, serif;"><span><span lang="en-US"><strong>Keywords</strong></span></span></span></p><p class="western" align="justify"><span style="font-family: Arial, serif;"><span><span lang="en-US">C</span></span></span><span style="font-family: Arial, serif;"><span><span lang="en-US">ollagen type IV; Laminin; </span></span></span><span style="font-family: Arial, serif;"><span><span lang="en-US">C</span></span></span><span style="font-family: Arial, serif;"><span><span lang="en-US">arcinoma; </span></span></span><span style="font-family: Arial, serif;"><span><span lang="en-US">I</span></span></span><span style="font-family: Arial, serif;"><span><span lang="en-US">mmunohistochemistry.</span></span></span></p><p> </p>

scholarly journals Expression of p53, bcl-2, and ki-67 Proteins in the Inflammatory Regenerative and Dysplastic Epithelial Lesions of Flat Colonic Mucosa

2008 ◽  
Vol 6 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Svjetlana Radović ◽  
Zora Vukobrat-Bijedić ◽  
Ivan Selak ◽  
Mirsad Babić
Keyword(s):  
Cellular Proliferation ◽  
P53 Protein ◽  
Normal Mucosa ◽  
Labelling Index ◽  
Epithelial Dysplasia ◽  
Severe Dysplasia ◽  
Ki 67 ◽  
Mild Dysplasia ◽  
Sporadic Cases ◽  
Epithelial Lesions

The aim of the study was to define the distribution of p53, bcl-2 and Ki-67 proteins in the inflammatory-regenerative and dysplastic lesionsof the colon mucosa. The relationship between the presentation of p53, bcl-2 and Ki-67 proteins and the intensity of the inflammatory-regenerative and dysplastic lesions in the colon flat mucosa was investigated as well. Biopsy specimens from 270 patients were examined: 74 were classified as inflammatory-regenerative and 196 as dysplastic lesions (108 mild, 58 moderate, and 30 severe dysplasia). The expression of all three proteins was assessed on the basis of location, quantity, and intensity of immunostaining, by counting antigen positive cells, in comparison with normal mucosa and adenocarcinoma. p53 protein appears only in sporadic cases (6.6%) of severe dysplasia. Bcl-2 expression appears significantly (p<0.005) more often in cases of mild dysplasia (61.1%) compared to inflammatory-regenerative mucosa (14.8%). In cases of mild dysplasia, bcl-2 positive cells were spreading from the lower third to the middle third of the crypts. Bcl-2 expression was maintained through the stadiums of moderate and severe dysplasia (75.8%), where antigen positive cells were found all along the crypts. A significant increase (p<0.005) in the expression of nuclear protein Ki-67 was noticed in the stadiums of moderate (labelling index =26.3) compared to mild dysplasia (labelling index=16.7), and severe (labelling index=36.7) compared to moderate dysplasia, where the zone of cellular proliferation was widen along the whole crypt length. In the process of the development of epithelial dysplasia in the flat mucosa of colon a degree of the gene p53 alteration is low and appears only in sporadic cases of severe dysplasia. Mutation of the bcl-2 gene is involved in the genesis of the lesion but not in its progression to carcinoma. Increased expressionof Ki-67 protein speaks in favour of an increased cellular proliferation which, together with the above mentioned mechanisms, is involved in the process of occurrence and progression of epithelial dysplasia in the flat mucosa of colon.

scholarly journals CCN3 controls 3D spatial localization of melanocytes in the human skin through DDR1

2006 ◽  
Vol 175 (4) ◽  
pp. 563-569 ◽  
Author(s):  
Mizuho Fukunaga-Kalabis ◽  
Gabriela Martinez ◽  
Zhao-Jun Liu ◽  
Jiri Kalabis ◽  
Paul Mrass ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Basal Layer ◽  
Spatial Localization ◽  
Collagen Iv ◽  
Collagen Type Iv ◽  
Matricellular Protein ◽  
Adhesion Receptor ◽  
Type Iv ◽  
Epidermal Homeostasis ◽  
Discoidin Domain Receptor 1

Melanocytes reside within the basal layer of the human epidermis, where they attach to the basement membrane and replicate at a rate proportionate to that of keratinocytes, maintaining a lifelong stable ratio. In this study, we report that coculturing melanocytes with keratinocytes up-regulated CCN3, a matricellular protein that we subsequently found to be critical for the spatial localization of melanocytes to the basement membrane. CCN3 knockdown cells were dissociated either upward to the suprabasal layers of the epidermis or downward into the dermis. The overexpression of CCN3 increased adhesion to collagen type IV, the major component of the basement membrane. As the receptor responsible for CCN3-mediated melanocyte localization, we identified discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase that acts as a collagen IV adhesion receptor. DDR1 knockdown decreased melanocyte adhesion to collagen IV and shifted melanocyte localization in a manner similar to CCN3 knockdown. These results demonstrate an intricate and necessary communication between keratinocytes and melanocytes in maintaining normal epidermal homeostasis.

scholarly journals Serum Anti-Collagen IV IgM and IgG Antibodies as Indicators of Low Vascular Turnover of Collagen IV in Patients with Long-Term Complications of Type 2 Diabetes

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 900
Author(s):  
Krasimir Kostov ◽  
Alexander Blazhev
Keyword(s):  
Type 2 Diabetes ◽  
Serum Levels ◽  
Vascular Wall ◽  
Collagen Iv ◽  
Collagen Type Iv ◽  
Non Invasive ◽  
Type Iv ◽  
Antibody Levels

Thickening of the vascular basement membrane (BM) is a fundamental structural change in the small blood vessels in diabetes. Collagen type IV (CIV) is a major component of the BMs, and monitoring the turnover of this protein in type 2 diabetes (T2D) can provide important information about the mechanisms of vascular damage. The aim of the study was through the use of non-invasive biomarkers of CIV (autoantibodies, derivative peptides, and immune complexes) to investigate vascular turnover of CIV in patients with long-term complications of T2D. We measured serum levels of these biomarkers in 59 T2D patients with micro- and/or macrovascular complications and 20 healthy controls using an ELISA. Matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) were also tested. In the T2D group, significantly lower levels of CIV markers and significantly higher levels of MMP-2 and MMP-9 were found compared to controls. A significant positive correlation was found between IgM antibody levels against CIV and MMP-2. These findings suggest that vascular metabolism of CIV is decreased in T2D with long-term complications and show that a positive linear relationship exists between MMP-2 levels and CIV turnover in the vascular wall.

scholarly journals Possible Implication of Intermolecular Epitope Spreading in the Production of Anti-Glomerular Basement Membrane Antibody in Anti-Neutrophil Cytoplasmic Antibody-associated Vasculitis

2021 ◽  
Author(s):  
Yuka Nishibata ◽  
Mayu Nonokawa ◽  
Yuto Tamura ◽  
Rio Higashi ◽  
Ku Suzuki ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Immunofluorescent Staining ◽  
Enzyme Linked Immunosorbent Assay ◽  
Collagen Type Iv ◽  
Normal Kidney ◽  
Type Iv ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Α3 Subunit

Abstract ObjectiveAnti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is sometimes complicated by anti-glomerular basement membrane (GBM) disease. Proteases, including elastase, released from neutrophils activated by ANCA are implicated in the pathogenesis of AAV. Epitopes of anti-GBM antibody exist in the α3-subunit non-collagenous (NC1) domain of collagen type IV [Col (IV)]. This region, called α3(IV)NC1, is structurally cryptic. This study aimed to determine the production mechanism of anti-GBM antibody in AAV.MethodsWe first examined whether α3(IV)NC1 could be revealed by the digestion of formalin-fixed, paraffin-embedded (FFPE) normal kidney sections and Col (IV) by proteases, including neutrophil elastase, using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). Next, the reveal of α3(IV)NC1 and the infiltration of CD11c+ macrophages in the affected kidneys were evaluated by IHC and immunofluorescent staining using FFPE sections. Finally, the production of anti-GBM antibody in AAV rats was determined by ELISA.Resultsα3(IV)NC1 was revealed by the digestion of FFPE normal kidney sections and Col (IV) by proteases. Although the reveal of α3(IV)NC1 was observed in sclerotic glomeruli regardless of causative diseases, CD11c+ macrophages near α3(IV)NC1 were characteristics of AAV. Anti-GBM antibody was produced subsequent to ANCA in some AAV rats. IHC demonstrated the reveal of α3(IV)NC1 in affected renal tissues and the infiltration of CD11c+ macrophages around the sites.ConclusionThe collective findings suggest that, in AAV, proteases released from neutrophils activated by ANCA digest Col (IV) and result in the reveal of α3(IV)NC1, CD11c+ macrophages present GBM epitopes, and then the host’s immune system produce anti-GBM antibody.

scholarly journals Expression of collagen type IV in human kidney during prenatal development

2020 ◽  
pp. 111-111
Author(s):  
Vladimir Petrovic ◽  
Ivan Nikolic ◽  
Marko Jovic ◽  
Vladimir Zivkovic ◽  
Miodrag Jocic ◽  
...  
Keyword(s):  
Type Iv Collagen ◽  
Collagen Type ◽  
Kidney Tissue ◽  
Volume Density ◽  
Collagen Iv ◽  
Basement Membranes ◽  
Collagen Type Iv ◽  
Type Iv ◽  
Metanephric Kidney ◽  
Collecting System

Background / Aim. Type IV collagen belongs to the group of non-fibrillar collagens and is an important component of the basement membranes where it accounts for approximately 50% of its structural elements. The aim of the paper was to describe the expression and distribution of collagen type IV in embryonic and fetal metanephric kidney, and to determine the volume density of collagen type IV in kidney tissue in each trimester of development. Methods. The material consisted of 19 human embryos/fetuses, in the gestational age from 8th to 37th week. Kidney tissue specimens were routinely processed to paraffin molds and stained with hematoxylin and eosin and immunohistochemically using polyclonal anti-collagen IV antibody. Stained slides were examined using light microscope and images of the selected areas, under different lens magnification were captured with digital camera. Volume density of collagen type IV was determined by using ImageJ 1.48v and a plugin of the software which inserted a grid system with 336 points. For the data comparison One-Way Analysis of Variance was used. Results. Strong collagen IV immunopositivity was seen in all specimens, with a distribution in the basement membranes of urinary bud, parietal leaf of Bowman?s capsule, glomerular basement membrane, basement membrane of interstitial blood vessels, and basement membranes of nephron tubules and collecting ducts. No statistically significant difference in the volume density of type IV collagen was found between the different trimesters of development. Conclusion. The synthesis and secretion of collagen type IV simultaneously follows the development of nephron structures, collecting system and blood vessels. The volume density of collagen type IV remains constant throughout all the trimesters of metanephric kidney development, indicating that it plays a crucial role in normal development of nephron and collecting system structures, as well as in maintaining the normal kidney function.

Specific ablation of the nidogen-binding site in the laminin γ1 chain interferes with kidney and lung development

Development ◽  
2002 ◽  
Vol 129 (11) ◽  
pp. 2711-2722 ◽  
Author(s):  
Michael Willem ◽  
Nicolai Miosge ◽  
Willi Halfter ◽  
Neil Smyth ◽  
Iris Jannetti ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Binding Site ◽  
Lung Development ◽  
Collagen Type Iv ◽  
Developmental Defects ◽  
Type Iv ◽  
And Function ◽  
Kidney Morphogenesis ◽  
Nidogen 1

Basement membrane assembly is of crucial importance in the development and function of tissues and during embryogenesis. Nidogen 1 was thought to be central in the assembly processes, connecting the networks formed by collagen type IV and laminins, however, targeted inactivation of nidogen 1 resulted in no obvious phenotype. We have now selectively deleted the sequence coding for the 56 amino acid nidogen-binding site, γ1III4, within the Lamc1 gene by gene targeting. Here, we show that mice homozygous for the deletion die immediately after birth, showing renal agenesis and impaired lung development. These developmental defects were attributed to locally restricted ruptures in the basement membrane of the elongating Wolffian duct and of alveolar sacculi. These data demonstrate that an interaction between two basement membrane proteins is required for early kidney morphogenesis in vivo.

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