Kidney fibrosis is the hallmark of chronic kidney disease (CKD) and is characterized by an imbalanced extracellular matrix (ECM) remodeling. Collagen type III is one of the main ECM components of the interstitial matrix of the kidney. We hypothesized that measuring three biomarkers of collagen type III reflecting different aspects of this protein turnover (C3M, C3C, and PRO-C3) may provide different information about the fibrotic burden in patients with IgA nephropathy (IgAN). We examined a cohort of 134 patients with IgAN. The three collagen type III biomarkers were measured in serum (S) and in urine (U) samples taken on the same day before kidney biopsy was performed. Biopsies were evaluated for interstitial fibrosis and tubular atrophy, according to the Banff and MEST-C scores. S-PRO-C3 and S-C3C correlated with the degree of fibrosis in the biopsy, whereas U-C3M/Cr had an inverse correlation with fibrosis. U-C3M/Cr had the highest discrimination ability for advanced fibrosis, which was maintained after adjustment for the other collagen type III biomarkers, proteinuria, and serum creatinine. The data presented in this study indicate that measuring the different fragments of the same ECM protein and in different matrices provides a variety of information regarding pathological kidney tissue alterations in patients with IgAN.
- Klíčová slova
- IgA nephropathy, biomarker, chronic kidney disease, collagen, extracellular matrix, fibrosis,
- MeSH
- biologické markery MeSH
- fibróza MeSH
- IgA nefropatie * patologie MeSH
- kolagen typ III MeSH
- komplement C3 analýza MeSH
- ledviny patologie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- kolagen typ III MeSH
- komplement C3 MeSH
Diabetic foot ulcer (DFU) is a serious complication of diabetes and hyperbaric oxygen therapy (HBOT) is also considered in comprehensive treatment. The evidence supporting the use of HBOT in DFU treatment is controversial. The aim of this work was to introduce a DFU model in ZDF rat by creating a wound on the back of an animal and to investigate the effect of HBOT on the defect by macroscopic evaluation, quantitative histological evaluation of collagen (types I and III), evaluation of angiogenesis and determination of interleukin 6 (IL6) levels in the plasma. The study included 10 rats in the control group (CONT) and 10 in the HBOT group, who underwent HBOT in standard clinical regimen. Histological evaluation was performed on the 18th day after induction of defect. The results show that HBOT did not affect the macroscopic size of the defect nor IL6 plasma levels. A volume fraction of type I collagen was slightly increased by HBOT without reaching statistical significance (1.35+/-0.49 and 1.94+/-0.67 %, CONT and HBOT, respectively). In contrast, the collagen type III volume fraction was ~120 % higher in HBOT wounds (1.41+/-0.81 %) than in CONT ones (0.63+/-0.37 %; p=0.046). In addition, the ratio of the volume fraction of both collagens in the wound ((I+III)w) to the volume fraction of both collagens in the adjacent healthy skin ((I+III)h) was ~65 % higher in rats subjected to HBOT (8.9+/-3.07 vs. 5.38+/-1.86 %, HBOT and CONT, respectively; p=0.028). Vessels density (number per 1 mm2) was found to be higher in CONT vs. HBOT (206.5+/-41.8 and 124+/-28.2, respectively, p<0.001). Our study suggests that HBOT promotes collagen III formation and decreases the number of newly formed vessels at the early phases of healing.
- MeSH
- diabetická noha metabolismus terapie MeSH
- hojení ran * MeSH
- hyperbarická oxygenace * MeSH
- kolagen typ III metabolismus MeSH
- krysa rodu Rattus MeSH
- náhodné rozdělení MeSH
- potkani Zucker MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- Názvy látek
- kolagen typ III MeSH
Dietary supplementation with polyunsaturated fatty acids (PUFA) n-3 can affect cutaneous wound healing; however, recent findings demonstrate the variable extent of their influence on the quality of healing. Here, we compare the effect of several dietary oils, containing different levels of PUFA n-3 and PUFA n-6, on wound healing in the rat model. Rats were fed the feed mixture with 8% palm oil (P), safflower oil (S), fish oil (F) or Schizochytrium microalga extract (Sch) and compared to the animals fed by control feed mixture (C). Dorsal full-thickness cutaneous excisions were performed after 52 days of feeding and skin was left to heal for an additional 12 days. Histopathological analysis of skin wounds was performed, including immune cells immunolabeling and the determination of hydroxyproline amount as well as gene expression analyses of molecules contributing to different steps of the healing. Matrix-assisted-laser-desorption-ionization mass-spectrometry-imaging (MALDI-MSI) was used to determine the amount of collagen α-1(III) chain fragment in healing samples. Treatment by Schizochytrium extract resulted in decrease in the total wound area, in contrast to the safflower oil group where the size of the wound was larger when comparing to control animals. Diet with Schizochytrium extract and safflower oils displayed a tendency to increase the number of new vessels. The number of MPO-positive cells was diminished following any of oil treatment in comparison to the control, but their highest amount was found in animals with a fish oil diet. On the other hand, the number of CD68-positive macrophages was increased, with the most significant enhancement in the fish oil and safflower oil group. Hydroxyproline concentration was the highest in the safflower oil group but it was also enhanced in all other analyzed treatments in comparison to the control. MALDI-MSI signal intensity of a collagen III fragment decreased in the sequence C > S > Sch > P > F treatment. In conclusion, we observed differences in tissue response during healing between dietary oils, with the activation of inflammation observed following the treatment with oil containing high eicosapentaenoic acid (EPA) level (fish oil) and enhanced healing features were induced by the diet with high content of docosahexaenoic acid (DHA, Schizochytrium extract).
- Klíčová slova
- MPO, collagen I/III, hydroxyproline, macrophages, mast cells, matrix-assisted-laser-desorption-ionization-mass-spectrometry-imaging, polyunsaturated fatty acids,
- MeSH
- antigeny CD8 metabolismus MeSH
- dietní tuky nenasycené aplikace a dávkování farmakologie MeSH
- hojení ran účinky léků MeSH
- indoly chemie MeSH
- kolagen typ III metabolismus MeSH
- krysa rodu Rattus MeSH
- kůže účinky léků zranění metabolismus MeSH
- kyseliny mastné omega-3 analýza MeSH
- kyseliny mastné omega-6 analýza MeSH
- makrofágy imunologie MeSH
- modely nemocí na zvířatech MeSH
- palmový olej aplikace a dávkování chemie farmakologie MeSH
- rybí oleje aplikace a dávkování chemie farmakologie MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
- světlicový olej aplikace a dávkování chemie farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- antigeny CD8 MeSH
- dietní tuky nenasycené MeSH
- indoly MeSH
- kolagen typ III MeSH
- kyseliny mastné omega-3 MeSH
- kyseliny mastné omega-6 MeSH
- palmový olej MeSH
- rybí oleje MeSH
- schizocommunin MeSH Prohlížeč
- světlicový olej MeSH
Local inflammation in axial spondyloarthritis (axSpA) leads to the release of collagen metabolites from the disease-affected tissue. We investigated whether collagen metabolites were associated with disease activity and could distinguish non-radiographic(nr)-axSpA from ankylosing spondylitis (AS). A total of 193 axSpA patients (nr-axSpA, n = 121 and AS, n = 72) and asymptomatic controls (n = 100) were included. Serum levels of metalloproteinase (MMP)-degraded collagen type I (C1M), type II (C2M), type III (C3M) and type IV (C4M2) were quantified by enzyme-linked immunosorbent assay (ELISA). All metabolites were higher in axSpA than in controls (all p < 0.001). Serum levels of C1M, C3M, and C4M2 were increased in AS compared to nr-axSpA (43.4 ng/mL vs. 34.6; p < 0.001, 15.4 vs. 12.8; p = 0.001, and 27.8 vs. 22.4; p < 0.001). The best metabolite to differentiate between axSpA and controls was C3M (AUC 0.95; specificity 92.0, sensitivity 83.4). C1M correlated with ASDAS-CRP in nr-axSpA (ρ = 0.37; p < 0.001) and AS (ρ = 0.57; p < 0.001). C1M, C3M, and C4M2 were associated with ASDAS-CRP in AS and nr-axSpA after adjustment for age, gender, and disease duration. Serum levels of collagen metabolites were significantly higher in AS and nr-axSpA than in controls. Moreover, the present study indicates that collagen metabolites reflect disease activity and are useful biomarkers of axSpA.
- MeSH
- ankylózující spondylitida krev diagnóza MeSH
- biologické markery krev MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- fibrilární kolageny metabolismus MeSH
- kolagen typ II metabolismus MeSH
- kolagen typ III metabolismus MeSH
- kolagen typu I metabolismus MeSH
- kolagen typu IV metabolismus MeSH
- lidé MeSH
- spondylartritida krev diagnóza MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- fibrilární kolageny MeSH
- kolagen typ II MeSH
- kolagen typ III MeSH
- kolagen typu I MeSH
- kolagen typu IV MeSH
One of the generally recognized factors contributing to the initiation and maintenance of atrial fibrillation (AF) is structural remodeling of the myocardium that affects both atrial cardiomyocytes as well as interstitium. The goal of this study was to characterize morphologically and functionally interstitium of atria in patients with AF or in sinus rhythm (SR) who were indicated to heart surgery. Patient population consisted of 46 subjects (19 with long-term persistent AF, and 27 in SR) undergoing coronary bypass or valve surgery. Peroperative bioptic samples of the left and the right atria were examined using immunohistochemistry to visualize and quantify collagen I, collagen III, elastin, desmin, smooth muscle actin, endothelium and Vascular Endothelial Growth Factor (VEGF). The content of interstitial elastin, collagen I, and collagen III in atrial tissue was similar in AF and SR groups. However, the right atrium was more than twofold more abundant in elastin as compared with the left atrium and similar difference was found for collagen I and III. The right atrium showed also higher VEGF expression and lower microvascular density as compared to the left atrium. No significant changes in atrial extracellular matrix fiber content, microvascular density and angiogenic signaling, attributable to AF, were found in this cohort of patients with structural heart disease. This finding suggests that interstitial fibrosis and other morphological changes in atrial tissue are rather linked to structural heart disease than to AF per se. Significant regional differences in interstitial structure between right and left atrium is a novel observation that deserves further investigation.
- MeSH
- elastin genetika metabolismus MeSH
- extracelulární matrix genetika metabolismus MeSH
- fibrilace síní metabolismus patologie patofyziologie MeSH
- kolagen typ III genetika metabolismus MeSH
- kolagen typu I genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- orgánová specificita MeSH
- senioři MeSH
- srdce - funkce síní MeSH
- srdeční frekvence * MeSH
- srdeční síně metabolismus patologie MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- elastin MeSH
- kolagen typ III MeSH
- kolagen typu I MeSH
The skin matrix metalloproteinase 3, tissue inhibitors of matrix metalloproteinase 2 and collagen III content changes in type 1 diabetes and insulin resistance treated with insulin and metformin were studied. Healthy adult male Wistar rats were obtained from experimental animal house, Department of Experimental Pharmacology, Medical University in Bialystok. The rats were divided randomly into five groups of 8 rats each. Control rats were injected intraperitoneally by NaCl. Type IDDM was induced by a single injection of Streptozocin. Insulin resistance was induced by a high-fat diet. The chosen groups of rats were also treated with insulin or metformin. ELISA Kits (USCN Life Science, China) were used to measure content of matrix metallo-proteinase 3 (ELISA Kit for Matrix Metalloproteinase 3 - MMP3), tissue inhibitor of matrix metalloproteinase 2 (ELISA Kit for Tissue Inhibitors of Metalloproteinase 2 - TIMP2) and content of collagen type 3 (ELISA Kit for Collagen Type III - COL3). The results were reported as a median. The statistical significance was defined as p<0.05. Type 1 diabetes and insulin resistance have significantly reduced the quality of the skin, shown by the increase in content of matrix metalloproteinase 3 and the decrease in content of tissue inhibitors of matrix metalloproteinase 2. Type 1 diabetes and insulin resistance have reduced the quality of the skin expressed by type III collagen content decrease but for future studies it is recommend to determine rat interstitial collagenase, MMP-13, as well. Insulin and metformin treatment improved the quality of the diabetic skin, demonstrated by the type III collagen content increase.
- MeSH
- diabetes mellitus 1. typu patofyziologie MeSH
- inzulin MeSH
- inzulinová rezistence MeSH
- kolagen typ III metabolismus MeSH
- kůže metabolismus patofyziologie MeSH
- matrixová metaloproteinasa 3 metabolismus MeSH
- metformin MeSH
- náhodné rozdělení MeSH
- pojivová tkáň patofyziologie MeSH
- potkani Wistar MeSH
- tkáňový inhibitor metaloproteinasy 2 metabolismus MeSH
- tkáňový inhibitor metaloproteinasy 3 metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- inzulin MeSH
- kolagen typ III MeSH
- matrixová metaloproteinasa 3 MeSH
- metformin MeSH
- tkáňový inhibitor metaloproteinasy 2 MeSH
- tkáňový inhibitor metaloproteinasy 3 MeSH
Previously, we found that treatment of cutaneous wounds with Atropa belladonna L. (AB) revealed shortened process of acute inflammation as well as increased tensile strength and collagen deposition in healing skin wounds (Gál et al. 2009). To better understand AB effect on skin wound healing male Sprague-Dawley rats were submitted to one round full thickness skin wound on the back. In two experimental groups two different concentrations of AB extract were daily applied whereas the control group remained untreated. For histological evaluation samples were removed on day 21 after surgery and stained for wide spectrum cytokeratin, collagen III, fibronectin, galectin-1, and vimentin. In addition, in the in vitro study different concentration of AB extract were used to evaluate differences in HaCaT keratinocytes proliferation and differentiation by detection of Ki67 and keratin-19 expressions. Furthermore, to assess ECM formation of human dermal fibroblasts on the in vitro level fibronectin and galectin-1 were visualized. Our study showed that AB induces fibronectin and galectin-1 rich ECM formation in vitro and in vivo. In addition, the proliferation of keratinocytes was also increased. In conclusion, AB is an effective modulator of skin wound healing. Nevertheless, further research is needed to find optimal therapeutic concentration and exact underlying mechanism of action.
- MeSH
- Atropa belladonna * chemie MeSH
- časové faktory MeSH
- extracelulární matrix účinky léků metabolismus MeSH
- fibroblasty účinky léků metabolismus patologie MeSH
- fibronektiny metabolismus MeSH
- galektin 1 metabolismus MeSH
- hojení ran účinky léků MeSH
- keratin-19 metabolismus MeSH
- keratinocyty účinky léků metabolismus patologie MeSH
- kolagen typ III metabolismus MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- kůže účinky léků zranění metabolismus patologie MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- penetrující rány farmakoterapie metabolismus patologie MeSH
- potkani Sprague-Dawley MeSH
- rostlinné extrakty chemie izolace a purifikace farmakologie MeSH
- rozpouštědla chemie MeSH
- vimentin metabolismus MeSH
- voda chemie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fibronektiny MeSH
- galektin 1 MeSH
- keratin-19 MeSH
- kolagen typ III MeSH
- rostlinné extrakty MeSH
- rozpouštědla MeSH
- vimentin MeSH
- voda MeSH
The aim of this study was to analyze the effect of indapamide and its combination with ACE inhibitor (captopril) and antioxidant (Provinols™) on both myocardial hypertrophy and fibrosis. Wistar rats were treated with L-NAME (40 mg/kg/day, L); L-NAME plus indapamide (1 mg/kg/day), or captopril (10 mg/kg/day), or Provinols™ (40 mg/kg/day), or combination of indapamide with captopril, and indapamide with Provinols™ for 7 weeks. Blood pressure (BP), LV hypertrophy and fibrosis were determined. The content of collagens type I and III was evaluated morphometrically after picrosirius red staining. L-NAME treatment led to increased BP, LV hypertrophy, total fibrosis and relative content of collagens without the change in collagen type I/III ratio. Indapamide and captopril decreased BP, LV hypertrophy and the collagen ratio without affecting total fibrosis, while Provinols™ reduced BP, the collagen ratio and fibrosis without affecting LV hypertrophy. The combinations decreased all the parameters. Decrease of LV hypertrophy was achieved by drugs with the best reducing effect on BP, fibrosis reduction was reached by the antioxidant treatment with only partial effect on BP. Thus, the combination of antihypertensive and antioxidant treatment may represent a powerful tool in preventing myocardial remodeling induced by hypertension.
- MeSH
- fibróza chemicky indukované metabolismus MeSH
- hypertenze chemicky indukované metabolismus MeSH
- hypertrofie levé komory srdeční metabolismus MeSH
- indapamid farmakologie MeSH
- kaptopril farmakologie MeSH
- kolagen typ III metabolismus MeSH
- kolagen typu I metabolismus MeSH
- krysa rodu Rattus MeSH
- myokard patologie MeSH
- NG-nitroargininmethylester škodlivé účinky MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- indapamid MeSH
- kaptopril MeSH
- kolagen typ III MeSH
- kolagen typu I MeSH
- NG-nitroargininmethylester MeSH
Increased amount of collagen type I and decreased amount of type III is described in various pathological processes in the vascular wall. Polyphenols were shown to have protective effect on endothelium, decrease blood pressure and prevent oxidative damage induced by various stimuli. Tetrachlormethane (CCl(4)) is a toxic substance with known negative systemic effects induced by free radicals. Chronic administration of CCl(4) for 12 weeks led to an increase of collagen type I and a decrease of type III in the wall of aorta. Parallel administration of red wine polyphenols significantly reduced the increase of collagen type I, at the same time the content of type III rose to the level above controls. After 4 weeks of spontaneous recovery no changes were observed. If polyphenols were administered during the recovery period, there was a decrease of type I and an increase of type III collagen content in the aorta. It can be concluded that polyphenols have a tendency to lower the amount of type I and to increase the proportion of type III collagen in the wall of the aorta. These changes are significant in prevention or in regression of changes induced by chronic oxidative stress. This effect of polyphenols is most likely the result of their influence on MMP-1 and TIMP activities through which they positively influence the collagen types I and III content ratio in the vascular wall in favor of the type III collagen.
- MeSH
- aorta účinky léků metabolismus MeSH
- chlorid uhličitý MeSH
- fenoly farmakologie MeSH
- flavonoidy farmakologie MeSH
- kolagen typ III metabolismus MeSH
- kolagen typu I metabolismus MeSH
- krysa rodu Rattus MeSH
- modely nemocí na zvířatech MeSH
- nemoci aorty chemicky indukované farmakoterapie metabolismus MeSH
- oxidační stres * MeSH
- polyfenoly MeSH
- potkani Wistar MeSH
- víno * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chlorid uhličitý MeSH
- fenoly MeSH
- flavonoidy MeSH
- kolagen typ III MeSH
- kolagen typu I MeSH
- polyfenoly MeSH
We studied the effect of thiazide-like diuretic--indapamide on fibrosis development in the left ventricle of young spontaneously hypertensive rats (SHR) and assessed the involvement of nitric oxide in this process. Six-week-old male SHR were treated with indapamide (1 mg/kg/day) for six weeks. Age-matched SHR were used as hypertensive and Wistar-Kyoto rats (WKY) as normotensive control. Systolic blood pressure was measured by tail-cuff plethysmography. Nitric oxide synthase (NOS) activity, protein expressions of endothelial (eNOS) and inducible NOS (iNOS), myocardial fibrosis and collagen type I and III were determined in the left ventricle. Indapamide treatment partially prevented SBP increase in SHR (SHR+Indapamide: 157+/-4, SHR: 171+/-3, WKY: 119+/-3 mmHg). Indapamide prevented myocardial fibrosis development in SHR, but without affecting collagen type I to type III ratio. Indapamide did not affect NOS activity as well as eNOS and iNOS protein expressions in the left ventricles evaluated by both Western blot and immunohistochemically. In conclusion, our results indicate that indapamide-induced prevention of myocardial fibrosis is not mediated by nitric oxide-related mechanism.
- MeSH
- azosloučeniny MeSH
- barvicí látky MeSH
- diuretika terapeutické užití MeSH
- fibróza MeSH
- funkce levé komory srdeční účinky léků fyziologie MeSH
- indapamid terapeutické užití MeSH
- kardiomyopatie metabolismus patologie prevence a kontrola MeSH
- kolagen typ III metabolismus MeSH
- kolagen typu I metabolismus MeSH
- krevní tlak fyziologie MeSH
- krysa rodu Rattus MeSH
- myokard enzymologie metabolismus patologie MeSH
- oxid dusnatý fyziologie MeSH
- potkani inbrední SHR MeSH
- potkani inbrední WKY MeSH
- remodelace komor fyziologie MeSH
- synthasa oxidu dusnatého, typ III metabolismus MeSH
- volné radikály metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- azosloučeniny MeSH
- barvicí látky MeSH
- C.I. direct red 80 MeSH Prohlížeč
- diuretika MeSH
- indapamid MeSH
- kolagen typ III MeSH
- kolagen typu I MeSH
- oxid dusnatý MeSH
- synthasa oxidu dusnatého, typ III MeSH
- volné radikály MeSH
