Pattern Of Collagen Deposition Research Articles

Immunohistochemical characteristics of collagen I, III, IV type deposition in the dynamics of progressing of the basic types of liver fibrosis in patients with non-alcohol steatohepatitis.

Background. The study of patterns of collagen deposition of various types in the dynamics of hepatic fibrosis progression is essential to the development of targeted therapy for liver fibrosis in patients with nonalcoholic and alcoholic steatohepatitis. Objective. The aim is to study the area of deposition of collagen I, III and IV type in the dynamics of the progression of F 1 - F 3 perisinusoidal-pericellular and portal-perisinusoidal fibrosis in F 4 liver cirrhosis of micronodular and pericellular type in hepatotrepanobioptates of patients with nonalcoholic steatohepatitis, using the methods of immunohistochemistry. Methods. The immunohistochemical studies are conducted in liver trepanobioptates in 80 patients with perisinusoidal pericellular and portal perisinusoidal fibrosis of varying severity. Results. It is found that the deposition of type I, III and IV collagen increases with the development and progression of fibrosis from F1 – the weak grade, to F2 –the moderate grade and F3 to severe grade of fibrosis in the liver. With the progression of perisinusoidal pericellular and portal perisinusoidal fibrosis, the increase in type III collagen deposition decreases. In F4 liver fibrosis/cirrhosis of the pericellular type, the deposition of type I and IV collagen reaches a maximum, the area of deposition of type I collagen is more than 50% greater than the deposition area of type III collagen. In F4 fibrosis/cirrhosis of the portal perisinusoidal type, the deposition area of type I collagen also reaches a maximum, while the collagen storage area of type III and IV stabilizes at the level of severe F3 of liver fibrosis. Conclusion. In patients with nonalcoholic steatohepatitis, the quantitative ratios of different types of collagen in the zones of perisinusoidal pericellular and portal perisinusoidal fibrosis change dynamically as the hepatofibrosis increase and its transformation into liver cirrhosis.

Hydroxylase inhibition regulates inflammation-induced intestinal fibrosis through the suppression of ERK-mediated TGF-β1 signaling. [corrected

Fibrosis is a complication of chronic inflammatory disorders such as inflammatory bowel disease, a condition which has limited therapeutic options and often requires surgical intervention. Pharmacologic inhibition of oxygen-sensing prolyl hydroxylases, which confer oxygen sensitivity upon the hypoxia-inducible factor pathway, has recently been shown to have therapeutic potential in colitis, although the mechanisms involved remain unclear. Here, we investigated the impact of hydroxylase inhibition on inflammation-driven fibrosis in a murine colitis model. Mice exposed to dextran sodium sulfate, followed by a period of recovery, developed intestinal fibrosis characterized by alterations in the pattern of collagen deposition and infiltration of activated fibroblasts. Treatment with the hydroxylase inhibitor dimethyloxalylglycine ameliorated fibrosis. TGF-β1 is a key regulator of fibrosis that acts through the activation of fibroblasts. Hydroxylase inhibition reduced TGF-β1-induced expression of fibrotic markers in cultured fibroblasts, suggesting a direct role for hydroxylases in TGF-β1 signaling. This was at least in part due to inhibition of noncanonical activation of extracellular signal-regulated kinase (ERK) signaling. In summary, pharmacologic hydroxylase inhibition ameliorates intestinal fibrosis through suppression of TGF-β1-dependent ERK activation in fibroblasts. We hypothesize that in addition to previously reported immunosupressive effects, hydroxylase inhibitors independently suppress profibrotic pathways.

TCDD Inhibits Heart Regeneration in Adult Zebrafish

Normal adult zebrafish can completely regenerate lost myocardium following partial amputation of the ventricle apex. We report that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) significantly impairs this regeneration. Adult male zebrafish were injected with vehicle (control) or TCDD (70ng/g, ip) 1 day prior to partial amputation of the ventricle apex. Gross observation and histological analysis of the amputated heart at 21 days postamputation revealed that TCDD-exposed fish had not progressed beyond the initial clot formation stage, whereas the vehicle control fish showed substantial recovery and almost complete resolution of the formed clot. In contrast, hearts that were not surgically wounded showed no signs of TCDD toxicity. Striking features in the TCDD-exposed hearts were the absence of the normal sheath of new tissue enveloping the wound and the absence of intense cell proliferation at the site of the wound. In addition, the patterns of collagen deposition at the wound site were different between the TCDD and vehicle groups. Because the receptor for TCDD is the aryl hydrocarbon receptor ligand-activated transcriptional regulator, we examined the effects of TCDD exposure on gene expression in the ventricle using DNA microarrays. Samples were collected just prior to amputation and at 6h and 7 days postamputation. TCDD-pretreated hearts had dysregulated expression of genes involved in heart function, tissue regeneration, cell growth, and extracellular matrix. Because embryonic, but not adult, hearts are major targets for TCDD-induced cardiotoxicity, we speculate that the need for embryonic-like cells in regeneration is connected with the effects of TCDD in inhibiting the response to wounding.

The intradermal anatomy of the inframammary fold.

The anatomy of the inframammary fold has been a subject of controversy. This report describes the anatomic location and the histologic structure of the inframammary fold on the basis of caderveric dissections and microscopic examination. Ten breast cadaver dissections were performed on female cadavers (ages 35 to 72). Twenty specimens after en bloc resections of the inframammary fold and subcutaneous tissue, including the pectoralis muscle, were harvested. Specimens were examined for gross collagen stricture by using India ink to highlight the collagenous aspects of the subcutaneous soft-tissue networks. The inframammary fold skin and dermis from the contralateral breast and control samples of skin and dermis from the upper chest and the abdomen were collected for microscopic studies. These samples were stained with Sirius red and examined microscopically by polarized light. On histologic examination, regular arrays of collagen were found running parallel with the inframammary fold, and the control sections showed random patterns of collagen deposition. On gross examination, a condensation of the superficial fascial system was observed. This formed a zone of adherence between the skin and the underlying pectoralis fascia. The conclusion of this study is that the inframammary fold is an intrinsic dermal structure consisting of regular arrays of collagen held in place by a zone of adherence that is a specialized area of the superficial fascial system. The clinical significance of this study is that the intradermal structure of the inframammary fold should be preserved in any breast procedure for natural aesthetic results.

Clinical significance of interstitial collagen deposition at the invading edge in oral cancer: Immunohistochemistry for type I collagen

Background Changes in interstitial collagen in human oral cancer have not yet been fully studied. We examined the relationship between the degree of interstitial collagen deposition at the invading edge of the tumor, and the clinical and pathologic findings in oral squamous cell carcinoma. We also investigated the therapeutic implication of the changes in distribution patterns of collagen deposition by comparing biopsy specimens and surgical specimens.

Evidence for Rapid Accumulation and Persistently Disordered Architecture of Fibrillar Collagen in Human Coronary Restenosis Lesions

The pattern of collagen deposition after coronary angioplasty could significantly influence recurrent lesion formation. Traditional histologic assessments of coronary restenosis lesions have not identified abundant collagen fibers in restenotic tissue; however, these methods can suffer from lack of sensitivity and are not quantitative. We analyzed collagen architecture in 40 coronary lesions retrieved from patients by directional atherectomy, by exploiting the birefringent properties of fibrillar collagen. Picrosirius red-stained sections were illuminated with circularly polarized light, and fiber content and thickness were quantified by digital image analysis. Fifteen of 19 restenosis lesions (79%) and 1 of 21 native atherosclerosis lesions (5%) displayed a pattern of reactive intimal modeling, characterized by stellate-shaped smooth muscle cells variably oriented in a loose extracellular matrix. There was an apparent paucity of collagen fibers in these regions based on staining with Movat's pentachrome, a traditional connective tissue stain. However, circular polarization light microscopy revealed an extensive distribution of collagen fibers in restenosis tissue, occupying 79.9% ± 11.8% of the section area. Despite this high collagen content, the restenosis lesions were distinct from de novo atherosclerosis lesions in having a disordered collagen alignment, reduced fiber packing (p <0.05), and thinner fibers (4.3 ± 1.7 vs 9.2 ± 4.3 μm, p <0.001). Fiber diameter was greater in lesions retrieved between 3 and 17 months after angioplasty than in lesions retrieved between 1 week and 3 months (p <0.05). However, fiber disorientation was evident in all lesions retrieved after 1 week, with little similarity to that of native plaque. Lesions retrieved within 1 week of angioplasty represented a distinct group with identical collagen features as in de novo atherosclerosis lesions, implying a different mechanism of restenosis in that population. We conclude that human coronary restenosis involves rapid accumulation of collagen fibers, which are persistently disordered. This may be critical in the development of restenosis and could significantly influence therapeutic attempts to control the process. (Am J Cardiol 1996;78:633–637)

Immunohistochemical localization of growth factors in fetal wound healing

Fetal wound healing occurs rapidly, in a regenerative fashion, and without scar formation, by contrast with adult wound healing, where tissue repair results in scar formation which limits tissue function and growth. The extracellular matrix deposited in fetal wounds contains essentially the same structural components as that in the adult wound but there are distinct differences in the spatial and temporal distribution of these components. In particular the organization of collagen in the healed fetal wound is indistinguishable from the normal surrounding tissue. Rapidity of healing, lack of an inflammatory response, and an absence of neovascularization also distinguish fetal from adult wound healing. The mechanisms controlling these differing processes are undefined but growth factors may play a critical role. The distribution of growth factors in healing fetal wounds is unknown. We have studied, by immunohistochemistry, the localization of platelet-derived growth factor (PDGF), transforming growth factor beta (TGF beta), and basic fibroblast growth factor (bFGF), in fetal, neonatal, and adult mouse lip wounds. TGF beta and bFGF were present in neonatal and adult wounds, but were not detected in the fetal wounds, while PDGF was present in fetal, neonatal, and adult wounds. This pattern correlates with the known effects in vitro of these factors, the absence of an inflammatory response and neovascularization in the fetal wound, and the patterns of collagen deposition in both fetal and adult wounds. The results suggest that it may be possible to manipulate the adult wound to produce more fetal-like, scarless, wound healing.

Scanning electron microscopy and gel electrophoresis of vascularized periosteal autografts.

This study was devised to investigate the morphologic and biochemical sequence of events occurring during early periosteal osteogenesis in vascularized periosteal flaps. A pleuroperiosteal flap based on the intercostal vessels was developed and rotated onto the chest wall in 12 adult dogs. Animals were sacrificed at intervals between 7 and 60 days, and the flaps were removed with the underlying muscular bed. Specimens were studied by tetracycline uptake, gel electrophoresis, light microscopy, and the scanning electron microscope. Osteoprogenitor cells were seen as early as 7 days after transfer. Collagen fiber deposition was vigorous and noted in all specimens with rapid mineralization by 9 to 15 days. There was no structural or vascular interaction between the flaps and the recipient muscular bed. Gel electrophoresis confirmed the presence of type I and III collagen, with an increase in type I collagen over time. The pattern of collagen deposition and the final bony architecture resembled that of woven bone.