scholarly journals An Ehrlich chromogen in collagen cross-links

1983 ◽  
Vol 209 (1) ◽  
pp. 263-264 ◽  
Author(s):  
J E Scott ◽  
R G Qian ◽  
W Henkel ◽  
R W Glanville
Keyword(s):  
Type Iv Collagen ◽  
Rich Source ◽  
Type Iii Collagen ◽  
Cross Link ◽  
Type Iii ◽  
Human Type ◽  
Type Iv ◽  
Cross Links

A well-characterized three-chain peptide [(Col1)2 X T9] from human type III collagen was a rich source of Ehrlich chromogen. The corresponding two-chain peptide [(Col1)2] was not, implying that the Ehrlich chromogen is a trifunctional cross-link. (Col1)2 X T9 also contained pyridinoline, which is not an Ehrlich chromogen. The 7S domain of type IV collagen also contained an Ehrlich chromogen.

Distribution of laminin and collagens during avian neural crest development

Development ◽  
1987 ◽  
Vol 101 (3) ◽  
pp. 461-478 ◽  
Author(s):  
J.L. Duband ◽  
J.P. Thiery
Keyword(s):  
Cell Migration ◽  
Neural Crest ◽  
Type Iv Collagen ◽  
Type I Collagen ◽  
Neural Crest Cell ◽  
Type Iii Collagen ◽  
Type I ◽  
Type Iii ◽  
Type Iv ◽  
Crest Cell

The distribution of type I, III and IV collagens and laminin during neural crest development was studied by immunofluorescence labelling of early avian embryos. These components, except type III collagen, were present prior to both cephalic and trunk neural crest appearance. Type I collagen was widely distributed throughout the embryo in the basement membranes of epithelia as well as in the extracellular spaces associated with mesenchymes. Type IV collagen and laminin shared a common distribution primarily in the basal surfaces of epithelia and in close association with developing nerves and muscle. In striking contrast with the other collagens and laminin, type III collagen appeared secondarily during embryogenesis in a restricted pattern in connective tissues. The distribution and fate of laminin and type I and IV collagens could be correlated spatially and temporally with morphogenetic events during neural crest development. Type IV collagen and lamin disappeared from the basal surface of the neural tube at sites where neural crest cells were emerging. During the course of neural crest cell migration, type I collagen was particularly abundant along migratory pathways whereas type IV collagen and laminin were distributed in the basal surfaces of the epithelia lining these pathways but were rarely seen in large amounts among neural crest cells. In contrast, termination of neural crest cell migration and aggregation into ganglia were correlated in many cases with the loss of type I collagen and with the appearance of type IV collagen and laminin among the neural crest population. Type III collagen was not observed associated with neural crest cells during their development. These observations suggest that laminin and both type I and IV collagens may be involved with different functional specificities during neural crest ontogeny. (i) Type I collagen associated with fibronectins is a major component of the extracellular spaces of the young embryo. Together with other components, it may contribute to the three-dimensional organization and functions of the matrix during neural crest cell migration. (ii) Type III collagen is apparently not required for tissue remodelling and cell migration during early embryogenesis. (iii) Type IV collagen and laminin are important components of the basal surface of epithelia and their distribution is consistent with tissue remodelling that occurs during neural crest cell emigration and aggregation into ganglia.

scholarly journals Blood-based extracellular matrix biomarkers are correlated with clinical outcome after PD-1 inhibition in patients with metastatic melanoma

2020 ◽  
Vol 8 (2) ◽  
pp. e001193
Author(s):  
Daan P Hurkmans ◽  
Christina Jensen ◽  
Stijn L W Koolen ◽  
Joachim Aerts ◽  
Morten Asser Karsdal ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Clinical Outcome ◽  
Metastatic Melanoma ◽  
Type Iv Collagen ◽  
Type Iii Collagen ◽  
Cox Regression Analysis ◽  
High Baseline ◽  
Type Iii ◽  
Type Iv ◽  
M1 Macrophage

BackgroundImmune checkpoint inhibitors that target the programmed cell death protein 1 (PD-1) receptor induce a response in only a subgroup of patients with metastatic melanoma. Previous research suggests that transforming growth factor beta signaling and a collagen-rich peritumoral stroma (tumor fibrosis), may negatively interfere with the interaction between T cells and tumor cells and thereby contribute to resistance mechanisms by immune-exclusion, while increased tumor infiltration of M1-like macrophages enhances T cell activity. Hence, the current study aimed to assess the relationship between blood-based markers of collagen or vimentin turnover (reflecting M1 macrophage activity) and clinical outcome in patients with metastatic melanoma after PD-1 inhibition.MethodsPatients with metastatic melanoma who were treated with anti-PD-1 monotherapy between May 2016 and March 2019 were included in a prospective observational study. N-terminal pro-peptide of type III collagen (PRO-C3) cross-linked N-terminal pro-peptides of type III collagen (PC3X), matrix metalloprotease (MMP)-degraded type III (C3M) and type IV collagen (C4M), granzyme B-degraded type IV collagen and citrullinated and MMP-degraded vimentin (VICM) were measured with immunoassays in serum before (n=107), and 6 weeks after the first administration of immunotherapy (n=94). The association between biomarker levels and overall survival (OS) or progression-free survival (PFS) was assessed.ResultsMultivariate Cox regression analysis identified high baseline PRO-C3 (Q4) and PC3X (Q4) as independent variables of worse PFS (PRO-C3: HR=1.81, 95% CI=1.06 to 3.10, p=0.030 and PC3X: HR=1.86, 95% CI=1.09 to 3.18, p=0.023). High baseline PRO-C3 was also independently related to worse OS (HR=2.08, 95% CI=1.06 to 4.09, p=0.035), whereas a high C3M/PRO-C3 ratio was related to improved OS (HR=0.42, 95% CI=0.20 to 0.90, p=0.025). An increase in VICM (p<0.0001; in 56% of the patients) was observed after 6 weeks of treatment, and an increase in VICM was independently associated with improved OS (HR=0.28, 95% CI=0.10 to 0.77, p=0.014).ConclusionsBlood-based biomarkers reflecting excessive type III collagen turnover were associated with worse OS and PFS after PD-1 inhibition in metastatic melanoma. Moreover, an increase in VICM levels after 6 weeks of treatment was associated with improved OS. These findings suggest that type III collagen and vimentin turnover contribute to resistance/response mechanisms of PD-1 inhibitors and hold promise of assessing extracellular matrix-derived and stroma-derived components to predict immunotherapy response.

Synthesis of type III Collagen and type IV collagen by tubular epithelial cells in diabetic nephropathy

1995 ◽  
Vol 191 (11) ◽  
pp. 1099-1104 ◽  
Author(s):  
M.S. Razzaque ◽  
T. Koji ◽  
Y. Horita ◽  
M. Nishihara ◽  
T. Harada ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Epithelial Cells ◽  
Type Iv Collagen ◽  
Type Iii Collagen ◽  
Tubular Epithelial Cells ◽  
Type Iii ◽  
Type Iv

scholarly journals P047 Differences in extra cellular matrix remodelling in highly active Crohn’s disease and ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S156-S157
Author(s):  
V Domislović ◽  
J H Mortensen ◽  
M A Karsdal ◽  
M Brinar ◽  
T Manon-Jensen ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Type Iv Collagen ◽  
Collagen Degradation ◽  
Type Iii Collagen ◽  
Collagen Turnover ◽  
Collagen Formation ◽  
Type Iii ◽  
Highly Active ◽  
Type Iv

Abstract Background Ulcerative colitis (UC) and Crohn’s disease (CD) require continuous evaluation of disease activity and response to therapy. Current gold standard is endoscopy; therefore it is important to investigate biomarkers associated with endoscopic disease activity. Extra cellular matrix (ECM) consists of basement membrane (BM) and interstitial matrix (IM). BM consists mainly of type IV collagen, while IM of types I, III and V collagen. Pathological environment leads to impaired remodelling, structure, quality and function of the ECM. We investigated biomarkers of collagen degradation and formation and their association with endoscopic disease activity and in patients with CD and UC. Methods In this cross-sectional study, we measured six biomarkers of ECM remodelling in 94 IBD patients (60 with CD and 34 UC). Biomarkers of type III collagen degradation (C3M) and formation (PRO-C3), type IV collagen degradation (C4M), formation (PRO-C4), type V collagen formation (PRO-C5) and PROC23 were measured in serum by ELISA. Inflammatory activity was measured using endoscopic scores; SES-CD for CD, MES and modified MES (mMES) for UC. Patients were divided in remission and mild activity group vs. moderate-to-severe activity (SES-CD &lt; 3 vs. ≥3 and MES &lt; 2 vs. ≥2) Student t-test and correlation analysis were applied in statistical analysis. Results CD patients with moderate and severe disease had lower levels of PRO-C3 (14.7 ± 10.5 vs. 9.9 ± 4.6, p = 0.04), and higher levels of C4M (26.54 ± 10.5 vs. 37.8 ± 20, p = 0.009) compared with patients in remission and mild disease. Biomarker of type III collagen turnover (C3M/PROC3) showed higher levels in moderate and severe active disease in CD (1 ± 0.5 vs. 1.8 ± 1.1, p = 0.006). UC patients with moderate to severe activity showed higher levels of type III collagen turnover biomarker (C3M/PROC3) (1.1 ± 0.4 vs. 1.97 ± 1, p = 0.049). C4M correlated positively (r = 0.28, p = 0.03) and PRO-C3 correlated negatively (r = −0.29, p = 0.03) to SES-CD and combined in a multivariate regression model (r = 0.39, p = 0.009). C3M (r = 0.60, p = 0.004) and C4M (r = 0.36, p = 0.039) correlated positively with mMES. Conclusion In highly active CD, there is increased type IV collagen degradation and reduced type III collagen formation. Both biomarkers significantly correlate with SES-CD, with increased correlation when combined together. Type III collagen turnover is increased in highly active CD and UC. Biomarkers of types III and IV collagen degradation correlate significantly with mMES. Biomarkers of types III and IV collagen could be used to differentiate highly active CD from UC. Our findings suggest that biomarkers of basement membrane and interstitial matrix remodelling may be used as surrogate markers for monitoring of disease activity for UC and CD.

scholarly journals Immunoelectron microscopic localization of laminin, type IV collagen, and type III pN-collagen in reticular fibers of human lymph nodes.

1989 ◽  
Vol 37 (3) ◽  
pp. 279-286 ◽  
Author(s):  
T Karttunen ◽  
R Sormunen ◽  
L Risteli ◽  
J Risteli ◽  
H Autio-Harmainen
Keyword(s):  
Basement Membrane ◽  
Lymph Nodes ◽  
Blood Vessels ◽  
Type Iv Collagen ◽  
Type Iii Collagen ◽  
Type Iii ◽  
Amino Terminal ◽  
Type Iv ◽  
Reticular Fibers ◽  
Collagenous Fibers

We studied the ultrastructural distribution of laminin, type IV collagen, and the amino terminal pro-peptide of type III collagen (type III pN-collagen) in normal human lymph nodes. After fixation with freshly prepared 4% paraformaldehyde mixed with 0.1% glutaraldehyde, cryoultramicrotomy proved to preserve the antigenicity of these proteins better than embedding in Lowicryl K4M. Sections were treated with rabbit antibodies against the 7S domain of human type IV collagen, the fragment P1 of human laminin, and the amino terminal pro-peptide of human type III pro-collagen, followed by anti-rabbit IgG conjugated to 10-nm colloidal gold. Laminin and type IV collagen were seen in the basement membrane structures of the blood vessels and in the walls of sinuses. The amorphous material between the collagenous fibers in locations corresponding to reticular fibers also contained laminin and type IV collagen. The amino terminal pro-peptide of type III pro-collagen was present in the collagenous fibers in reticular fibers and in the walls of blood vessels and sinuses. Therefore, a significant number of the type III collagen molecules in these fibers must have retained their amino terminal pro-peptide. These results indicate that the basement membrane proteins laminin and type IV collagen are genuine components of reticular fibers, as suggested earlier by immunohistochemical studies at the light microscopic level.

Binding Of VWF To Type IV Collagen: An Additional Collagen Binding Mechanism Beyond Types I, III, and VI Collagen?

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 333-333
Author(s):  
Veronica H. Flood ◽  
Joan Cox Gill ◽  
Sandra L. Haberichter ◽  
Daniel B Bellissimo ◽  
Pamela A Christopherson ◽  
...  
Keyword(s):  
Type Iv Collagen ◽  
Type Iii Collagen ◽  
Healthy Controls ◽  
Type Vi Collagen ◽  
Collagen Binding ◽  
Type Iii ◽  
Type Iv ◽  
Sequence Variations ◽  
The Mean

Abstract Von Willebrand disease (VWD) is a common bleeding disorder characterized by defects in the interaction of von Willebrand factor (VWF) with its ligands factor VIII, platelet glycoprotein Ib, and/or collagen. Nearly all assessment of collagen binding is performed with types I or III collagen. Type VI collagen, which is formed as a tight triple helix, has also been reported to interact with VWF. In contrast, type IV collagen lacks this tight helical structure and is located in the basal lamina. Type IV collagen may therefore serve as another important ligand for VWF. We examined this interaction in samples from the Zimmerman Program for the Molecular and Clinical Biology of VWD, a large US study of subjects with all types of VWD. Subjects were enrolled based on a pre-existing diagnosis of VWD and compared to a cohort of healthy controls. VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), and type III collagen binding using 1 mcg/mL human placental type III collagen (VWF:CB3) were performed in the clinical laboratory at the BloodCenter of Wisconsin. Type IV and type VI collagen binding (VWF:CB4 and VWF:CB6) were performed in the research laboratory by ELISA using 1 mcg/mL human placental type IV or type VI collagen captured on amine binding plates. DNA sequencing was performed on all subjects to identify VWF sequence variations. Bleeding scores were calculated according to the scoring system used in the MCMDM-1VWD study. For this analysis, 251 healthy controls, 535 type 1, 49 type 2A, 16 type 2B, 18 type 2M, 11 type 2N, and 18 type 3 VWD were included. The mean VWF:CB4/VWF:Ag ratio for the healthy controls was 0.96, with a standard deviation of 0.24. This was similar to the mean VWF:CB6/VWF:Ag ratio (mean 0.95, p=NS), but slightly lower than the mean VWF:CB3/VWF:Ag ratio (mean 1.05, p<0.01). The mean VWF:CB4/VWF:Ag ratio was 0.87 for the type 1 VWD subjects. The mean VWF:CB4/VWF:Ag ratio was significantly lower in type 1 subjects as compared to healthy controls (p<0.01). This was attributed in part to the presence of several A1 domain sequence variations, including p.R1399H, p.F1369I, and p.L1382P. While the latter sequence variations were isolated findings in single subjects, p.R1399H was present in 1% of the healthy controls, 1% of the type 1, and 6% of the type 2M VWD subjects. Mean VWF:CB4/VWF:Ag ratios were low for both type 2A and type 2B VWD subjects, at 0.54 and 0.52 respectively. This was not significantly different from the VWF:CB3/VWF:Ag data (p=NS for both type 2A and 2B VWD), consistent with the loss of high molecular weight multimers in these subjects and the concomitant reduction in collagen binding. As expected, VWF:CB4/VWF:Ag ratios were normal in the type 2N subjects, with a mean of 1.04. The type 2M subjects, however, displayed a significant reduction in type IV collagen binding, with a mean VWF:CB4/VWF:Ag ratio of 0.79. One subject with an 11 amino acid deletion (from p.R1392 through p.Q1402) had absent binding to type IV collagen yet normal binding to type III collagen with a VWF:CB3/VWF:Ag ratio of 0.82. Another subject with p.I1425F and p.R1399H had a VWF:CB4/VWF:Ag ratio of 0.48, and VWF:CB3/VWF:Ag ratio of 1.10. Type IV collagen binding did not correlate with VWF:RCo (R squared less than 0.1). The type 2M subjects with a mean VWF:CB4/VWF:Ag ratio less than 0.7 had higher bleeding scores, with a mean bleeding score of 9 compared to a mean of 6 for type 2M subjects with a mean VWF:CB4/VWF:Ag ratio greater than 0.7. Not surprisingly, the subjects with type 3 VWD and undetectable VWF:Ag also had undetectable VWF:CB4. These data suggest that type IV collagen binding reflects an independent function of VWF apart from platelet binding, and distinct from binding to type III collagen. In our study, more variation was seen between type IV and type III collagen than between type IV and type VI collagen. Neither VWF:CB4 nor VWF:CB6 are currently tested as part of the clinical workup of VWD. Measurement of this function may assist in identification of variant VWD, particularly in the subgroup of patients with type 2M VWD. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Cross-link analysis of the C-telopeptide domain from type III collagen

1996 ◽  
Vol 318 (2) ◽  
pp. 497-503 ◽  
Author(s):  
W. HENKEL
Keyword(s):  
Sequence Analysis ◽  
Cross Linking ◽  
Type Iii Collagen ◽  
Cross Link ◽  
Type Iii ◽  
C Terminus ◽  
Collagen Iii ◽  
Cross Links ◽  
The Cross ◽  
Helical Region

Several peptides were isolated from tryptic digests of insoluble calf aorta matrix by chromatography. Reductive pyridylethylation of a tryptic 15 kDa pool released fragments deriving from the C-terminus of type III collagen. A 50-residue peptide TC(III) was shown by sequence analysis to be the C-terminal peptide from the α1(III)-chain, containing a helical and non-helical region of equal sizes. The peptide was further digested with collagenase to give ColC(III), comprising the complete C-terminal non-helical region of α1(III) including a hydroxylysine in position 16C. The peptide TC(III)×TN(III) was isolated, demonstrating covalent cross-linking between the C-terminal non-helical region of one type III molecule and the N-terminal helical cross-linking region of another. Its digestion with cyanogen bromide yielded the small fragments α1(III)CB3B* and α1(III)CB3C, confirming TN(III) as an N-terminal helical cross-link site. Sequence analysis of both TC(III)×TN(III) and its collagenase-derived cross-linked peptide ColC(III)×TN(III) established the 4D-staggered alignment of adjacent collagen III molecules. The cross-link structure of both peptides was mainly dihydroxylysinonorleucine with a small amount of hydroxylysinonorleucine, indicating that the lysine residues involved in formation of the cross-links are both hydroxylated. No pyridinoline or histidinohydroxylysinonorleucine cross-links were found within the non-reduced C-telopeptide region of type III collagen.

Increased serum concentration of type IV collagen peptide and type III collagen peptide in hyperthyroidism

1992 ◽  
Vol 205 (3) ◽  
pp. 181-186 ◽  
Author(s):  
Takehiro Inui ◽  
Yukio Ochi ◽  
Wen Chen ◽  
Yoshiyuki Nakajima ◽  
Yoshihiro Kajita
Keyword(s):  
Serum Concentration ◽  
Type Iv Collagen ◽  
Type Iii Collagen ◽  
Type Iii ◽  
Collagen Peptide ◽  
Type Iv

scholarly journals Chemistry of collagen cross-links: glucose-mediated covalent cross-linking of type-IV collagen in lens capsules

1993 ◽  
Vol 296 (2) ◽  
pp. 489-496 ◽  
Author(s):  
A J Bailey ◽  
T J Sims ◽  
N C Avery ◽  
C A Miles
Keyword(s):  
Type Iv Collagen ◽  
Cross Linking ◽  
Mechanical And Thermal Properties ◽  
Maximum Strain ◽  
Scanning Calorimetry ◽  
Melting Temperatures ◽  
Type Iv ◽  
Collagen Molecules ◽  
Cross Links

The incubation of lens capsules with glucose in vitro resulted in changes in the mechanical and thermal properties of type-IV collagen consistent with increased cross-linking. Differential scanning calorimetry (d.s.c.) of fresh lens capsules showed two major peaks at melting temperatures Tm 1 and Tm 2 at approx. 54 degrees C and 90 degrees C, which can be attributed to the denaturation of the triple helix and 7S domains respectively. Glycosylation of lens capsules in vitro for 24 weeks caused an increase in Tm 1 from 54 degrees C to 61 degrees C, while non-glycosylated, control incubated capsules increased to a Tm 1 of 57 degrees C. The higher temperature required to denature the type-IV collagen after incubation in vitro suggested increased intermolecular cross-linking. Glycosylated lens capsules were more brittle than fresh samples, breaking at a maximum strain of 36.8 +/- 1.8% compared with 75.6 +/- 6.3% for the fresh samples. The stress at maximum strain (or ‘strength’) was dramatically reduced from 12.0 to 4.7 N.mm.mg-1 after glycosylation in vitro. The increased constraints within the system leading to loss of strength and increased brittleness suggested not only the presence of more cross-links but a difference in the location of these cross-links compared with the natural lysyl-aldehyde-derived cross-links. The chemical nature of the fluorescent glucose-derived cross-link following glycosylation was determined as pentosidine, at a concentration of 1 pentosidine molecule per 600 collagen molecules after 24 weeks incubation. Pentosidine was also determined in the lens capsules obtained from uncontrolled diabetics at a level of about 1 per 100 collagen molecules. The concentration of these pentosidine cross-links is far too small to account for the observed changes in the thermal and mechanical properties following incubation in vitro, clearly indicating that another as yet undefined, but apparently more important cross-linking mechanism mediated by glucose is taking place.

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