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Collagen Accumulation (collagen + accumulation)
Selected AbstractsRegional distribution of collagen and haemosiderin in the lungs of horses with exercise-induced pulmonary haemorrhageEQUINE VETERINARY JOURNAL, Issue 6 2009F. J. Derksen Summary Reasons for performing study: Regional veno-occlusive remodelling of pulmonary veins in EIPH-affected horses, suggests that pulmonary veins may be central to pathogenesis. The current study quantified site-specific changes in vein walls, collagen and haemosiderin accumulation, and pleural vascular profiles in the lungs of horses suffering EIPH. Hypothesis: In the caudodorsal lung regions of EIPH-affected horses, there is veno-occlusive remodelling with haemosiderosis, angiogenesis and fibrosis of the interstitium, interlobular septa and pleura. Methods: Morphometric methods were used to analyse the distribution and accumulation of pulmonary collagen and haemosiderin, and to count pleural vascular profiles in the lungs of 5 EIPH-affected and 2 control horses. Results: Vein wall thickness was greatest in the dorsocaudal lung and significantly correlated with haemosiderin accumulation. Increased venous, interstitial, pleural and septal collagen; lung haemosiderin; and pleural vascular profiles occurred together and changes were most pronounced in the dorsocaudal lung. Further, haemosiderin accumulation colocalised with decreased pulmonary vein lumen size. Vein wall thickening, haemosiderin accumulation and histological score were highly correlated and these changes occurred only in the caudodorsal part of the lung. Conclusion: The colocalisation of these changes suggests that regional (caudodorsal) venous remodelling plays an important role in the pathogenesis of EIPH. Potential relevance: The results support the hypothesis that repeated bouts of venous hypertension during strenuous exercise cause regional vein wall remodelling and collagen accumulation, venous occlusion and pulmonary capillary hypertension. Subjected to these high pressures, there is capillary stress failure, bleeding, haemosiderin accumulation and, subsequently, lung fibrosis. [source] High dietary methionine plus cholesterol stimulates early atherosclerosis and late fibrous cap development which is associated with a decrease in GRP78 positive plaque cellsINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 3 2009Anthony Zulli Summary The role of homocysteine, or its precursor methionine, in the formation of fibrous caps and its association with endoplasmic reticulum (ER) stress is unclear. Homocysteine can stimulate collagen accumulation and upregulate the ER stress chaperone glucose regulated protein 78 (GRP78). The aim of this study was to determine if high dietary methionine would increase fibrous caps, and that removal of an atherogenic diet would decrease the amount of ER stressed cells. New Zealand white rabbits were fed for 2, 4, or 12 weeks an atherogenic diet [1% methionine + 0.5% cholesterol (2MC, 4MC or 12MC)]; for 4 or 12 weeks a 0.5% cholesterol diet (4Ch, 12Ch); and to study plaque regression, an MC diet for 2 or 4 weeks accompanied by 10 weeks of a normal diet (2MCr, 4MCr). Endothelial function, atherosclerosis and GRP78 positive cells were studied. Endothelial function was abolished in 4MC and atherosclerosis increased 17-fold (P < 0.05) compared with 4Ch. Fibrous caps composed 48% of total plaque area in 12MC vs. 10% in 12Ch (P < 0.01), and 12MC expressed less GRP78 plaque cells vs. 12Ch (P < 0.01). Four MCr had less plaque GRP78 cells than 12MC (P < 0.05) and less endothelial GRP78 cells (P < 0.01). In addition, GRP78 positive cells were the highest in 4MC, but decreased in all other groups (P < 0.01). GRP78 positive cells within the fibrous cap inversely correlated with cap size (r2 = 0.9). These studies suggest that high dietary methionine could be beneficial for plaque stabilisation, and a normal diet also stabilises plaque and decreases the number of stressed plaque cells. [source] Ascorbic Acid Induces Collagenase-1 in Human Periodontal Ligament Cells but Not in MC3T3-E1 Osteoblast-Like Cells: Potential Association Between Collagenase Expression and Changes in Alkaline Phosphatase Phenotype,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2003Momotoshi Shiga Abstract Ascorbic acid (AA) enhances osteoblastic differentiation by increasing collagen accumulation, which in turn, results in increased alkaline phosphatase (AP) expression in some osteogenic cells. However, in other cells, including human periodontal ligament (PDL) cells, additional osteoinductive agents are required for this response. To understand the potential basis for the maintenance of the AP phenotype of PDL cells exposed to AA, we examined the modulation of the tissue-degrading matrix metalloproteinases (MMPs) and their inhibitors by AA in short-term cell cultures. Early passage PDL cells in serum-free medium were exposed to AA for 5 days. The samples were analyzed for MMPs and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), AP, collagen I(,1), and osteocalcin. We found that AA dose-dependently increased the expression of collagenase-1, and minimally TIMP-1, but not stromelysin-1 or TIMP-2. Additionally, AA caused substantial increases in levels of type I collagen. AA was unable to increase AP activity or osteocalcin messenger RNA in PDL cells. However, the cells retained the ability to show a significantly greater AP expression in high- versus low-density cultures, and increased osteocalcin as well as AP levels when cultured in the presence of dexamethasone. Moreover, in cells exposed to dexamethasone, increases in AP and osteocalcin were accompanied by a repression of collagenase-1 expression. In contrast to PDL cells, AA did not induce collagenase but produced a significant increase in AP expression in MC3T3-E1 cells. These findings provide the first evidence that AA, by modulating both collagen and collagenase-1 expression in PDL cells, most likely contributes to a net matrix remodeling response in these cells. Furthermore, the relationship between changes in collagenase expression and alterations in AP activity in PDL and MC3T3-E1 cells suggests a potential role for collagenase in modulating the AP phenotype of cells with osteoblastic potential. [source] Flutamide inhibits nifedipine- and interleukin-1,-induced collagen overproduction in gingival fibroblastsJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2010H.-K. Lu Lu H-K, Tseng C-C, Lee Y-H, Li C-L, Wang L-F. Flutamide inhibits nifedipine- and interleukin-1,-induced collagen overproduction in gingival fibroblasts. J Periodont Res 2010; 45: 451,457. © 2010 John Wiley & Sons A/S Background and Objective:, To understand the role of the androgen receptor in gingival overgrowth, the effects of flutamide on interleukin-1,- and nifedipine-induced gene expression of connective tissue growth factor (CTGF/CCN2) and collagen production in gingival fibroblasts were examined. Material and Methods:, Gingival fibroblasts from healthy subjects and patients with dihydropyridine-induced gingival overgrowth (DIGO) were used. Confluent cells were treated with nifedipine, interleukin-1, or both. The mRNA expression was examined using real-time polymerase chain reaction, and the concentration of total soluble collagen in conditioned media was analysed by Sircol Collagen Assay. In addition, the protein expressions of androgen receptor, CTGF/CCN2 and type I collagen in gingival tissue were determined by western blot. Results:, Interleukin-1, was more potent than nifedipine in stimulating CTGF/CCN2 and procollagen ,1(I) mRNA expression, and there was an additive effect of the two drugs. Healthy cells exhibited an equal or stronger response of procollagen ,1(I) than those with DIGO, but DIGO cells displayed a stronger response in the secretion of soluble collagen in the same conditions. Flutamide, an androgen receptor antagonist, inhibited stimulation by nifedipine or interleukin-1,. Additionally, the protein expressions of androgen receptor and type I collagen were higher in DIGO gingival tissue than those in healthy gingival tissue. Conclusion:, The data suggest that both nifedipine and interleukin-1, play an important role in DIGO via androgen receptor upregulation and that gingival overgrowth is mainly due to collagen accumulation. Flutamide decreases the gene expression and protein production of collagen from dihydropyridine-induced overgrowth cells. [source] Evaluation by scanning acoustic microscopy (SAM) on glomerular lesion of IgA nephropathyNEPHROLOGY, Issue 2001H Kiyomoto IgA nephropathy (IgAN) is known to commonly cause of end-stage renal failure in Japan. The glomerular lesions of IgAN have histological variations. The determination of prognosis and therapeutic strategy should be carefully done by experts because morphological information from renal biopsies using ordinary optical microscopy is usually qualitative and subjective. Moreover, the histological items for the evaluation of glomerular lesions seems to be unsatisfactory for expression of the disease condition of IgAN. The beneficial properties of scanning acoustic microscopy (SAM) include not only observation of microstructure but also quantitative measurement of acoustic propagation speed (APS), indicating the tissue elasticity. In the present study we compared the APS of glomeruli with the pathological scores that were determined by ordinary light microscopy. We used stocked human renal biopsy specimens diagnosed as IgAN (n = 12) and normal/minimal changes (n = 5). All samples were taken by renal biopsy in Kagawa Medical University Hospital during 1997,2000 under informed consent of the patients. The obtained renal tissue were immersed in 10% formalin and embedded in paraffin. A fixed specimen was consecutively cut into 4 ,m slices. One of the deparaffinized 4 ,m-specimens was directly utilized for SAM without any staining, and the others were stained with haematoxylin-eosin and Masson Trichrome for counting cell number and evaluation of collagen accumulation. For the measurement of glomerular APS, the sample line was set on the equator of the glomerulus and then scanning of the X,Z axis was carried out to obtain the interference fringes that were analysed with a computer imaging software in order to calculate the APS. In light microscopic study, pathological scores were evaluated semiquantitatively by two independent investigators who were unaware of the sample number. Glomerular lesions were scored into five grades and glomerular cell number was also counted in individual glomerulus. The computer-assisted imaging analyser Win ROOF (Mitani, Fukui, Japan) was also used for the determination of glomerular collagen content in specimens stained by Masson Trichrome. A two-dimensional image (C-mode scanning) of SAM enabled imaging of glomerulus in renal biopsy specimen compatible with findings of ordinary light microscopy without staining dye. The glomerular APS in IgAN was significantly higher than in normal/minimal changes. This alteration of glomerular APS in IgAN was positively correlated to both semiquantitative pathological scores and glomerular collagen content determined by light microscopy. However, the cell number of glomelurus did not change between IgAN and normal/minimal change. As a result, we conclude that the glomerular lesion, especially matrix expansion in IgAN, was comparable with the absolute value among specimens. Therefore, it is suggested that SAM method is a novel and useful technique for quantitative evaluation of glomerular lesion in IgAN. [source] Effect of phenytoin on collagen accumulation by human gingival fibroblasts exposed to TNF- ,in vitroORAL DISEASES, Issue 2 2006T Kato Objective:, Tumor necrosis factor (TNF)- , is associated with chronic gingival inflammation and reported to induce gingival overgrowth (GO), while phenytoin (PHT) is also known to be a causative agent of GO. We examined the synergistic effect of PHT and TNF- , on collagen metabolism in human gingival fibroblasts (HGFs). Materials and methods:, HGFs were cultured with TNF- , and PHT. Quantitative real-time RT-PCR was employed to determine the mRNA levels for collagen, matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and integrin subunits. Cellular collagen endocytosis was determined using a flow-cytometry. Results:, The proliferation of HGFs was not affected by TNF- , or PHT individually, whereas both synergistically increased collagen accumulation in HGFs. Further, collagen mRNA expression was not increased by TNF- , or PHT, although together they markedly prevented cellular collagen endocytosis, associated with the suppression of ,2,1-integrin mRNA expression. The mRNA expression of MMP-1 and-2 was suppressed by PHT, while TIMP-1 mRNA expression was enhanced by both TNF- , and PHT. Conclusion:, Our results suggest that TNF- , and PHT together cause impaired collagen metabolism by suppression of enzymatic degradation with MMPs/TIMP-1 and integrin-mediated endocytosis. These synergistic effects may also be involved in TNF- , - and PHT-induced collagen accumulation, leading to GO. [source] Regulation of pulmonary inflammation and fibrosis through expression of integrins ,V,3 and ,V,5 on pulmonary T lymphocytesARTHRITIS & RHEUMATISM, Issue 5 2009Irina G. Luzina Objective Pulmonary diseases associated with fibrosis, including scleroderma lung disease, are characterized by the accumulation of T cells in the lungs. These cells are thought to facilitate lung fibrosis, but the exact mechanisms of their profibrotic action are not clear. Several ,V-containing integrins, including ,V,3 and ,V,5, have been shown to directly activate transforming growth factor , (TGF,) and promote collagen accumulation. The aim of this study was to investigate whether pulmonary T cells express profibrotic integrins and regulate collagen accumulation. Methods Expression of integrins was assessed by immunohistochemical analysis of lung tissue, by flow cytometry using bronchoalveolar lavage fluid from patients with systemic sclerosis (SSc), and in a CCL18 overexpression animal model of pulmonary T cell infiltration. Experiments in cell cultures were performed to determine whether integrin-expressing T cells are profibrotic in cocultures with pulmonary fibroblasts and, if so, through what possible mechanism. Results Lymphocytes and integrin-positive cells were present in the lungs, and pulmonary T cells expressed integrins ,V,3 and ,V,5 in patients with SSc and in the animal model. Systemic administration of neutralizing anti,integrin ,V antibody or a genetic deficiency of integrin ,3 in the CCL18 overexpression model significantly attenuated CCL18-driven pulmonary lymphocytic infiltration and collagen accumulation. Jurkat T cells overexpressing integrin ,V,3 or integrin ,V,5 in cocultures with primary pulmonary fibroblasts stimulated collagen accumulation and Smad2 nuclear translocation. Neutralizing anti-TGF, antibody attenuated the profibrotic effect of integrin-expressing T cells. Conclusion Pulmonary infiltrating T lymphocytes may express integrins ,V,3 and ,V,5 that are necessary for lymphocytic infiltration and T cell,associated TGF, activation and collagen accumulation. [source] Induction of prolonged infiltration of T lymphocytes and transient T lymphocyte,dependent collagen deposition in mouse lungs following adenoviral gene transfer of CCL18ARTHRITIS & RHEUMATISM, Issue 8 2006Irina G. Luzina Objective Levels of CCL18 are elevated in patients with scleroderma lung disease and other fibrotic pulmonary diseases associated with T lymphocyte involvement. We sought to determine whether CCL18 alone can induce pulmonary T lymphocytic infiltration and fibrosis in mouse lungs. Methods An adenovirus vector was constructed and used for CCL18 delivery to mouse lungs in vivo. Immunohistochemical, flow cytometric, and enzyme-linked immunosorbent assay analyses were used to assess the resulting changes. Results Overexpression of CCL18 led to massive perivascular and peribronchial infiltration of T lymphocytes. Although the expression of CCL18 peaked on day 7, the infiltration persisted up to day 64 after infection. The infiltrates were negative for proliferating cell nuclear antigen and TUNEL, suggesting the role of cell trafficking, rather than proliferation and apoptosis, in the infiltration dynamics. Patchy destruction of the alveolar architecture and collagen accumulation in association with the infiltrates were also noticed. These changes were infiltration-dependent, rather than CCL18-dependent, since treatment with antilymphocyte serum completely abrogated the CCL18-induced changes. The infiltrates consisted almost exclusively of T lymphocytes that were minimally activated, with a minimal increase in the expression of CD69 and no changes in the expression of CD25, Fas, FasL, or CD40L. There was no increase in total pulmonary levels of profibrotic cytokines transforming growth factor ,1 (TGF,1) or interleukin-13, although active TGF,1 was present locally in association with the infiltrates and areas of distorted alveolar architecture. Prestimulation of primary T lymphocytes with CCL18 in vitro caused an up-regulation of TGF,1 and collagen production in T lymphocyte/fibroblast cocultures. Conclusion CCL18 promotes selective, long-term pulmonary infiltration of T lymphocytes and infiltration-dependent accumulation of collagen through a TGF,1-dependent mechanism. [source] | ||||||||||