摘要 :
Background: Many types of glomerulonephritis (GN) undergo tandem connected phases: inflammation and fibrosis. Fibrosis in human GNs leads to irreversible end-stage disease. This study investigated how these 2 phases were controlle...
展开
Background: Many types of glomerulonephritis (GN) undergo tandem connected phases: inflammation and fibrosis. Fibrosis in human GNs leads to irreversible end-stage disease. This study investigated how these 2 phases were controlled. Methods: Using a rat anti-glomerular basement membrane GN model, we established bone marrow (BM) chimeras between GN-resistant Lewis (LEW) and GN-susceptible Wistar Kyoto (WKY) rats. Glomerular inflammation and fibrosis were compared between chimeras. Results: LEW's BM to WKY chimeras with or without co-transfer of host WKY's T cells were GN-resistant. On the other hand, WKY's BM to LEW (LEW WKY) chimeras developed glomerular inflammation and albuminuria upon immunization. Quantitative analysis showed that the number and composition of inflammatory cells in glomeruli of immunized LEW WKY chimeras were similar to those in immunized WKY rats at their inflammatory peak. Thus, glomerular inflammation was controlled by BM-derived non-T cell populations. However, unlike WKY rats, LEW WKY rats did not develop fibrosis until the end of experiments (84 days) in spite of persistent inflammation and albuminuria. Conclusion: Inflammation alone was not sufficient to trigger fibrosis, suggesting a critical role of glomerular cells in the fibrotic process. As LEW WKY chimera allows us to separate glomerular inflammation from fibrosis, this model provides a useful tool to study how fibrosis is initiated following inflammation. (C) 2015 S. Karger AG, Basel
收起
摘要 :
Scleroderma is characterized by vascular injury and increased production and accumulation of extracellular matrix proteins by activated fibroblasts in the skin of patients with immunologic abnormalities. A growing body of evidence...
展开
Scleroderma is characterized by vascular injury and increased production and accumulation of extracellular matrix proteins by activated fibroblasts in the skin of patients with immunologic abnormalities. A growing body of evidence has demonstrated that extracellular matrix overproduction in the sclerotic dermis by scleroderma fibroblasts results from complex interactions among endothelial cells, immunocytes and fibroblasts, mediated by various cytokines, chemokines and their receptors. Recently, novel signaling pathways leading to fibrosis have been clarified and genomic analysis have also been progressing. In tandem with investigation of human scleroderma, animal models are indispensable for a better understanding of the pathomechanisms of scleroderma, and a number of animal models have been developed. In this review, current insights into the pathophysiology of dermal sclerosis and therapeutic approaches are discussed.
收起
摘要 :
Intestinal fibrosis is a common outcome in IBD leading to significant morbidity that, to date, has no effective medical treatment. Current knowledge regarding potential mechanism(s) of intestinal fibrogenesis and stricture formati...
展开
Intestinal fibrosis is a common outcome in IBD leading to significant morbidity that, to date, has no effective medical treatment. Current knowledge regarding potential mechanism(s) of intestinal fibrogenesis and stricture formation is limited, due in large part to the lack of relevant animal models. Although conventional models possess aspects that are advantageous to study specific mechanisms involved in gut fibrosis, most lack the features of a spontaneously occurring process leading to the formation of intestinal fibrotic lesions following mucosal inflammatory events and the ability to investigate the natural course of disease over time. This review aims to discuss established and novel animal models of gut fibrosis, particularly focusing on the advantages and disadvantages of each model system and the insights they bring to our understanding of the mechanisms of fibrogenesis. In fact, recent enhancements to existing models and the expansion of novel animal models of gut fibrosis is opening up multiple avenues for investigation which should stimulate progress in our mechanistic understanding of intestinal fibrogenesis and facilitate the development of effective pharmacotherapy in an area of significant unmet need. (C) 2014 S. Karger AG, Basel
收起
摘要 :
Purpose We aimed to determine the time, dose, and volume responses in a mouse pulmonary injury model following ablative dose focal irradiation (ADFIR) in order to better understand normal lung injury.
摘要 :
Aim: This study is presenting an effective method of inducing liver fibrosis by CCL4 as a toxin in two different breeds of rat models. Background: Liver fibrosis is a result of inflammation and liver injury caused by wound healing...
展开
Aim: This study is presenting an effective method of inducing liver fibrosis by CCL4 as a toxin in two different breeds of rat models. Background: Liver fibrosis is a result of inflammation and liver injury caused by wound healing responses which ultimately lead to liver failure. Consequently, after liver fibrosis, the progression will be continued to liver cirrhosis and at the end stage hepatocellular carcinoma (HCC). Many studies have demonstrated that one of the most important causes of liver fibrosis is Non-alcoholic steatohepatitis (NASH). Fibrotic Liver is affected by an excessive accumulation of extracellular matrix (ECM) proteins like collagen and α-SMA. Methods: In two different experiments, male Vistar, and Sprague Dawley Rat models ranging from 200±60, corresponding to an age of approximately 10 weeks were utilized in order to induce CCL4 treated liver fibrosis. Results: After 6 weeks of CCL4 injection, different tests have been carried out to verify the liver fibrosis including serum markers such as Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT), molecular tests containing, laminin and α-SMA and also pathological observation by Hematoxylin and eosin staining in both fibrosis and control group. Conclusion: The results of Pathology and Real-time PCR showed that fibrosis was induced much more effectively in Sprague Dawley rat model compared with Wistar rats.
收起
摘要 :
Combined pulmonary fibrosis and emphysema (CPFE) is a recently recognized syndrome that, as its name indicates, involves the existence of both interstitial lung fibrosis and emphysema in one individual, and is often accompanied by...
展开
Combined pulmonary fibrosis and emphysema (CPFE) is a recently recognized syndrome that, as its name indicates, involves the existence of both interstitial lung fibrosis and emphysema in one individual, and is often accompanied by pulmonary hypertension. This debilitating, progressive condition is most often encountered in males with an extensive smoking history, and is presented by dyspnea, preserved lung volumes, and contrastingly impaired gas exchange capacity. The diagnosis of the disease is based on computed tomography imaging, demonstrating the coexistence of emphysema and interstitial fibrosis in the lungs, which might be of various types and extents, in different areas of the lung and several relative positions to each other. CPFE bears high mortality and to date, specific and efficient treatment options do not exist. In this review, we will summarize current knowledge about the clinical attributes and manifestations of CPFE. Moreover, we will focus on pathophysiological and pathohistological lung phenomena and suspected etiological factors of this disease. Finally, since there is a paucity of preclinical research performed for this particular lung pathology, we will review existing animal studies and provide suggestions for the development of additional in vivo models of CPFE syndrome.
收起
摘要 :
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive scarring interstitial lung disease with an unknown cause. Some patients may experience acute exacerbations (AE), which result in severe lung damage visible on imaging o...
展开
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive scarring interstitial lung disease with an unknown cause. Some patients may experience acute exacerbations (AE), which result in severe lung damage visible on imaging or through examination of tissue samples, often leading to high mortality rates. However, the etiology and pathogenesis of AE-IPF remain unclear. AE-IPF patients exhibit diffuse lung damage, apoptosis of type II alveolar epithelial cells, and an excessive inflammatory response. Establishing a reliable animal model of AE is critical for investigating the pathogenesis. Recent studies have reported a variety of animal models for AE-IPF, each with its own advantages and disadvantages. These models are usually established in mice with bleomycin-induced pulmonary fibrosis, using viruses, bacteria, small peptides, or specific drugs. In this review, we present an overview of different AE models, hoping to provide a useful resource for exploring the mechanisms and targeted therapies for AE-IPF.
收起
摘要 :
Objective Irreversible electroporation (IRE) uses microsecond-long electric pulses to kill cells through membrane permea-bilization, without affecting surrounding extracellular structures. We evaluated whether IRE can be used to i...
展开
Objective Irreversible electroporation (IRE) uses microsecond-long electric pulses to kill cells through membrane permea-bilization, without affecting surrounding extracellular structures. We evaluated whether IRE can be used to induce urinary obstruction for a rat model of renal scarring. Materials and methods Intrasurgical IRE (2000 V/cm, 90 pulses, 100 |is) with caliper electrodes was performed in the right proximal ureter in male rats (n = 24) which were euthanized at 2, 5, or 10 days post-treatment, following contrast-enhanced magnetic resonance imaging. Complete urinary tract (bilateral kidneys, ureter and bladder) was extracted, and scored on a five-point scale for renal dilation, ureteral dilation and hydronephrosis. Whole kidney sections underwent immunohistochem-istry to quantify levels of macrophages (CD68), activated fibroblasts [α-smooth muscle actin (α-SMA)], collagen (Masson's Trichrome) and Hematoxylin and Eosin. Change in renal pelvis diameter and the number of glomeruli in the treated and contralateral urinary tract was also computed. Results Intrasurgical IRE performed with non-invasive caliper electrodes resulted in immediate loss of peristalsis in the treated ureteral segment, and cell death in the ureteral muscularis along with urothelial sloughing. Dilation of the ureter was observed on gross anatomic evaluation and histopathology. Magnetic resonance imaging indicated partial stricture and urinary obstruction in IRE-treated urinary tract, without evidence of urinoma, leakage or fistula formation. Enlargement of the kidney with progressive renal dilation and hydronephrosis was evident between Day 2 and Day 10 post-treatment. Obstructed kidney demonstrated scarring with elevated levels of tissue collagen, macrophages and α-SMA-positive fibroblasts. There was a steady decrease in the number of glomeruli in the obstructed kidney, while glomeruli numbers in the contralateral kidney remained unchanged through the 10-day observation period. Conclusion IRE provides a safe and reproducible technique to induce partial ureteral obstruction and renal fibrosis in rat model without the need for ligation or its associated complications.
收起
摘要 :
Systemic sclerosis (SSc) is a devastating chronic autoimmune connective tissue disease characterized by vasculopathy, autoimmunity with inflammation, and progressive fibrogenesis. The current paradigm of the pathogenesis of SSc is...
展开
Systemic sclerosis (SSc) is a devastating chronic autoimmune connective tissue disease characterized by vasculopathy, autoimmunity with inflammation, and progressive fibrogenesis. The current paradigm of the pathogenesis of SSc is that of an unknown initial trigger, leading to a complex interaction of immune cells, endothelial cells, and fibroblasts, producing cytokines, growth and angiogenic factors, and resulting in uncontrolled and persistent tissue fibrogenesis by an altered mesenchymal cell compartment. Animal models are of utmost importance to investigate the different steps in the pathogenesis. This review will elaborate on recent findings in established and more recently developed animal models, presenting data on compounds that are in or ready to be translated into clinical trials, or provide interesting new findings in the understanding of the pathophysiology of SSc. We focus on recent findings concerning the vessel-extracellular matrix interaction, the initial triggering aggressor, the concept of autoimmunity and inflammatory changes, the effector cells and their origins, and the complex interaction of the different signaling pathways in fibrogenesis.
收起