Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Interstitial collagen catabolism.

ABSTRACT: Interstitial collagen mechanical and biological properties are altered by proteases that catalyze the hydrolysis of the collagen triple-helical structure. Collagenolysis is critical in development and homeostasis but also contributes to numerous pathologies. Mammalian collagenolytic enzymes include matrix metalloproteinases, cathepsin K, and neutrophil elastase, and a variety of invertebrates and pathogens possess collagenolytic enzymes. Components of the mechanism of action for the collagenolytic enzyme MMP-1 have been defined experimentally, and insights into other collagenolytic mechanisms have been provided. Ancillary biomolecules may modulate the action of collagenolytic enzymes.

SUBMITTER: Fields GB

PROVIDER: S-EPMC3610953 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Effect of molecular size on interstitial pharmacokinetics and tissue catabolism of antibodies.

Project description:Advances in antibody engineering have enabled the construction of novel molecular formats in diverse shapes and sizes, providing new opportunities for biologic therapies and expanding the need to understand how various structural aspects affect their distribution properties. To assess the effect of antibody size on systemic pharmacokinetics (PK) and tissue distribution with or without neonatal Fc receptor (FcRn) binding, we evaluated a series of non-mouse-binding anti-glycoprotein D monoclonal antibody formats, including IgG [~150 kDa], one-armed IgG [~100 kDa], IgG-HAHQ (attenuated FcRn binding) [~150 kDa], F(ab')2 [~100 kDa], and F(ab) [~50 kDa]. Tissue-specific concentration-time profiles were corrected for blood content based on vascular volumes and normalized based on interstitial volumes to allow estimation of interstitial concentrations and interstitial:serum concentration ratios. Blood correction demonstrated that the contribution of circulating antibody on total uptake was greatest at early time points and for highly vascularized tissues. Tissue interstitial PK largely mirrored serum exposure profiles. Similar interstitial:serum ratios were obtained for the two FcRn-binding molecules, IgG and one-armed IgG, which reached pseudo-steady-state kinetics in most tissues. For non-FcRn-binding molecules, interstitial:serum ratios changed over time, suggesting that these molecules did not reach steady-state kinetics during the study. Furthermore, concentration-time profiles of both intact and catabolized molecule were measured by a dual tracer approach, enabling quantification of tissue catabolism and demonstrating that catabolism levels were highest for IgG-HAHQ. Overall, these data sets provide insight into factors affecting preclinical distribution and may be useful in estimating interstitial concentrations and/or catabolism in human tissues.

| S-EPMC9311319 | biostudies-literature

Autoantibody Profiles in Collagen Disease Patients with Interstitial Lung Disease

Project description:Auto-antibody (Ab) profiles between acute-onset diffuse ILD (AoDILD) and stable states of 25 collagen disease patients were compared to screen biomarkers or pathogenic auto-Abs.

2017-02-09 | GSE59687 | GEO

Collagen unfolding accelerates water influx, determining hydration in the interstitial matrix.

Project description:In the interstitial matrix, collagen unfolding at physiologic temperatures is thought to facilitate interactions with enzymes and scaffold molecules during inflammation, tissue remodeling, and wound healing. We tested the hypothesis that it also plays a role in modulating flows and matrix hydration potential. After progressively unfolding dermal collagen in situ, we measured the hydration parameters by osmotic stress techniques and modeled them as linear functions of unfolded collagen, quantified by differential scanning calorimetry after timed heat treatment. Consistent with the hypothetical model, the thermodynamic and flow parameters obtained experimentally were related linearly to the unfolded collagen fraction. The increases in relative humidity and intensity of T(2) maps were also consistent with interfacial energy contributions to the hydration potential and the hydrophobic character of the newly formed protein/water interfaces. As a plausible explanation, we propose that increased tension at interfaces formed during collagen unfolding generate local gradients in the matrix that accelerate water transfer in the dermis. This mechanism adds a convective component to interstitial transfer of biological fluids that, unlike diffusion, can speed the dispersion of water and large solutes within the matrix.

| S-EPMC3512047 | biostudies-literature

Collagen networks within 3D PEG hydrogels support valvular interstitial cell matrix mineralization.

Project description:Enzymatically degradable hydrogels were designed for the 3D culture of valvular interstitial cells (VICs), and through the incorporation of various functionalities, we aimed to investigate the role of the tissue microenvironment in promoting the osteogenic properties of VICs and matrix mineralization. Specifically, porcine VICs were encapsulated in a poly(ethylene glycol) hydrogel crosslinked with a matrix metalloproteinase (MMP)-degradable crosslinker (KCGPQG↓IWGQCK) and formed via a thiol-ene photoclick reaction in the presence or absence of collagen type I to promote matrix mineralization. VIC-laden hydrogels were treated with osteogenic medium for up to 15 days, and the osteogenic response was characterized by the expression of RUNX2 as an early marker of an osteoblast-like phenotype, osteocalcin (OCN) as a marker of a mature osteoblast-like phenotype, and vimentin (VIM) as a marker of the fibroblast phenotype. In addition, matrix mineralization was characterized histologically with Von Kossa stain for calcium phosphate. Osteogenic response was further characterized biochemically with calcium assays, and physically via optical density measurements. When the osteogenic medium was supplemented with calcium chloride, OCN expression was upregulated and mineralization was discernable at 12 days of culture. Finally, this platform was used to screen various drug therapeutics that were assessed for their efficacy in preventing mineralization using optical density as a higher throughput readout. Collectively, these results suggest that matrix composition has a key role in supporting mineralization deposition within diseased valve tissue.

| S-EPMC7738375 | biostudies-literature

Collagen biomarkers and subclinical interstitial lung disease: The Multi-Ethnic Study of Atherosclerosis.

Project description:BACKGROUND:Lung fibrosis is attributed to derangements in extracellular matrix remodeling, a process driven by collagen turnover. We examined the association of two collagen biomarkers, carboxy-terminal telopeptide of collagen type I (ICTP) and amino-terminal propeptide of type III procollagen (PIIINP), with subclinical interstitial lung disease (ILD) in adults. METHODS:We performed a cross-sectional analysis of 3244 participants age 45-84 years in the Multi-Ethnic Study of Atherosclerosis. Serum ICTP and PIIINP levels were measured at baseline by radioimmunoassay. Subclinical ILD was defined as high attenuation areas (HAA) in the lung fields on baseline cardiac CT scans. Interstitial lung abnormalities (ILA) were measured in 1082 full-lung CT scans at 9.5 years median follow-up. We used generalized linear models to examine the associations of collagen biomarkers with HAA and ILA. RESULTS:Median (IQR) for ICTP was 3.2??g/L (2.6-3.9??g/L) and for PIIINP was 5.3??g/L (4.5-6.2??g/L). In fully adjusted models, each SD increment in ICTP was associated with a 1.3% increment in HAA (95% CI 0.2-2.4%, p?=?0.02) and each SD increment in PIIINP was associated with a 0.96% increment in HAA (95% CI 0.06-1.9%, p?=?0.04). There was no association between ICTP or PIIINP and ILA. There was no evidence of effect modification by gender, race, smoking status or eGFR. CONCLUSIONS:Higher levels of collagen biomarkers are associated with greater HAA independent of gender, race and smoking status. This suggests that extracellular matrix remodeling may accompany subclinical ILD prior to the onset of clinically evident disease.

| S-EPMC6310068 | biostudies-literature

<Editors’ Choice> Comparison of clinical features between patients with acute exacerbation of idiopathic interstitial pneumonia and collagen vascular disease-associated interstitial pneumonia

Project description: Not available

| S-EPMC10565576 | biostudies-literature

Serum biomarker analysis of collagen disease patients with acute-onset diffuse interstitial lung disease.

Project description:BackgroundInterstitial lung disease (ILD) is frequently associated with collagen diseases. The prognosis of acute-onset diffuse ILD (AoDILD) occurring in collagen disease patients is very poor. Here, we investigated serum biomarker profiles of AoDILD to find markers predicting outcome in patients with collagen diseases.MethodsA solid-phase antibody array was used for screening 274 biomarkers in pooled sera from collagen disease patients in the AoDILD state and in the stable state. Biomarkers in individual sera were detected without pooling by bead-based immunoassay.ResultsThe serum levels of matrix metalloproteinase (MMP)-1, tissue inhibitor of metalloproteinase (TIMP)-1, osteopontin, interleukin (IL)-2 receptor ? (IL-2R?), and IL-1 receptor antagonist were significantly increased in AoDILD, but TIMP-2, MMP-3, and eotaxin 2 levels were decreased. The MMP-3 to MMP-1 ratio was reduced in AoDILD state. This tendency was also observed in RA patients with AoDILD. Moreover, serum IL-6 level was significantly increased in the AoDILD state in patients with acute exacerbation of ILD (AE-ILD). Serum TIMP-1 and IL-2R? levels were significantly increased in the AoDILD state in patients with drug-induced ILD (DI-ILD), whereas TIMP-2, MMP-3, and eotaxin 2 levels were decreased. The MMP-3 to MMP-1 ratio was reduced in AoDILD state in patients with DI-ILD. The serum TIMP-3, MMP-9, osteopontin, IL-2R?, MMP-1, and MMP-8 levels were significantly increased in the AoDILD state in patients who subsequently died, whereas TIMP-2 and MMP-3 levels were decreased in those who survived. The MMP-3 to MMP-1 ratio was reduced in AoDILD state in patients who died, but not in those who survived.ConclusionsSerum biomarker profiles could represent prognosis markers for AoDILD in collagen diseases.

| S-EPMC3598392 | biostudies-literature

Role of Deleterious Rare Alleles for Acute-Onset Diffuse Interstitial Lung Disease in Collagen Diseases.

Project description:ObjectiveAcute-onset diffuse interstitial lung disease (AoDILD) includes acute exacerbation of interstitial lung disease (ILD), drug-induced ILD, and Pneumocystis pneumonia in collagen diseases patients. As AoDILD causes a poor prognosis in collagen disease patients, the pathogenesis of AoDILD should be investigated. Exome sequencing studies revealed that rare variants were detected to be causative in some diseases. Recently reported upregulated genes in acute exacerbation of idiopathic pulmonary fibrosis could provide candidate genes for restricted exome analysis of AoDILD in collagen disease. Here, we investigated rare variants in the coding and boundary regions of these candidate genes in AoDILD.MethodsDeleterious rare variants in the coding and boundary regions of the candidate genes were analyzed by exome sequencing and the deleterious rare allele frequencies in AoDILD were compared with those of controls.ResultsA significant association was detected for deleterious rare alleles in NPL (P = .0044, P c = .0399, odds ratio [OR] = 10.05, 95% confidence interval [CI] = 3.01-33.55). A deleterious rare allele frequency in the 9 candidate genes (P = .0011, OR = 7.17, 95% CI = 2.80-18.33) was also increased in AoDILD in multigene panel analysis. The Krebs von den Lungen-6 (KL-6) levels in AoDILD patients with deleterious rare alleles were tended to be lower than those without (P = .0168, P c = .1509).ConclusionsThe deleterious rare alleles in NPL were associated with AoDILD. In addition, the deleterious rare allele frequency in the 9 candidate genes was also increased in AoDILD. The deleterious rare alleles might contribute to the pathogenesis of AoDILD.

| S-EPMC6668171 | biostudies-literature

Separation of Solid Stress From Interstitial Fluid Pressure in Pancreas Cancer Correlates With Collagen Area Fraction.

Project description:Elevated total tissue pressure (TTP) in pancreatic adenocarcinoma is often associated with stress applied by cellular proliferation and hydrated hyaluronic acid osmotic swelling; however, the causal roles of collagen in total tissue pressure have yet to be clearly measured. This study illustrates one direct correlation between total tissue pressure and increased deposition of collagen within the tissue matrix. This observation comes from a new modification to a conventional piezoelectric pressure catheter, used to independently separate and quantify total tissue pressure, solid stress (SS), and interstitial fluid pressure (IFP) within the same tumor location, thereby clarifying the relationship between these parameters. Additionally, total tissue pressure shows a direct correlation with verteporfin uptake, demonstrating the impediment of systemically delivered molecules with increased tissue hypertension.

| S-EPMC6993781 | biostudies-literature