Fibrogenesis & Tissue Repair最新文献_第9页

CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis. CTGF是组织重塑和纤维化的中心介质，其抑制可以逆转纤维化过程。

Fibrogenesis & Tissue Repair Pub Date : 2012-06-06 eCollection Date: 2012-01-01 DOI: 10.1186/1755-1536-5-S1-S24

Kenneth E Lipson, Carol Wong, Yuchin Teng, Suzanne Spong

{"title":"CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis.","authors":"Kenneth E Lipson, Carol Wong, Yuchin Teng, Suzanne Spong","doi":"10.1186/1755-1536-5-S1-S24","DOIUrl":"https://doi.org/10.1186/1755-1536-5-S1-S24","url":null,"abstract":"CTGF is a secreted matricellular protein with very complex biology. It has been shown to modulate many signaling pathways leading to cell adhesion and migration, angiogenesis, myofibroblast activation, and extracellular matrix deposition and remodeling, which together lead to tissue remodeling and fibrosis. It has been reported in the literature that inhibition of CTGF expression by siRNA prevents CCl4-induced liver fibrosis and can reverse fibrosis when administered after significant collagen deposition is observed. A monoclonal antibody to CTGF that is currently in clinical development (FG-3019) has demonstrated the ability to reverse vascular stiffening and improve cardiac function in a rat model of diabetic complications. FG-3019 has also exhibited activity in a murine radiation-induced pulmonary fibrosis model. When FG-3019 was administered to mice after a significant radiation-induced increase in lung density could be observed by CT imaging, the density of the lungs was observed to decrease over the period during which the antibody was administered and to remain stable after therapy had ceased. When considered together, these data indicate that inhibition of CTGF can prevent and reverse the process of fibrosis. ","PeriodicalId":12264,"journal":{"name":"Fibrogenesis & Tissue Repair","volume":"5 Suppl 1","pages":"S24"},"PeriodicalIF":0.0,"publicationDate":"2012-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1755-1536-5-S1-S24","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31140513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 442

The role of redox mechanisms in hepatic chronic wound healing and fibrogenesis. 氧化还原机制在肝脏慢性伤口愈合和纤维化中的作用。

Fibrogenesis & Tissue Repair Pub Date : 2012-06-06 eCollection Date: 2012-01-01 DOI: 10.1186/1755-1536-5-S1-S4

Erica Novo, Maurizio Parola

{"title":"The role of redox mechanisms in hepatic chronic wound healing and fibrogenesis.","authors":"Erica Novo, Maurizio Parola","doi":"10.1186/1755-1536-5-S1-S4","DOIUrl":"https://doi.org/10.1186/1755-1536-5-S1-S4","url":null,"abstract":"Under physiological conditions, intracellular and tissue levels of reactive oxygen species (ROS) are carefully controlled and employed as fine modulators of signal transduction, gene expression and cell functional responses (redox signaling). A significant derangement in redox homeostasis, resulting in sustained levels of oxidative stress and related mediators, plays a role in the pathogenesis of human diseases characterized by chronic inflammation, chronic activation of wound healing and tissue fibrogenesis, including chronic liver diseases. In this chapter major concepts and mechanisms in redox signaling will be briefly recalled to introduce a number of selected examples of redox-related mechanisms that can actively contribute to critical events in the natural history of a chronic liver diseases, including induction of cell death, perpetuation of chronic inflammatory responses and fibrogenesis. A major focus will be on redox-dependent mechanisms involved in the modulation of phenotypic responses of activated, myofibroblast-like, hepatic stellate cells (HSC/MFs), still considered as the most relevant pro-fibrogenic cells operating in chronic liver diseases. ","PeriodicalId":12264,"journal":{"name":"Fibrogenesis & Tissue Repair","volume":"5 Suppl 1","pages":"S4"},"PeriodicalIF":0.0,"publicationDate":"2012-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1755-1536-5-S1-S4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31135912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 54

Fibrocytes and the pathogenesis of diffuse parenchymal lung disease. 纤维细胞与弥漫性肺实质疾病的发病机制。

Fibrogenesis & Tissue Repair Pub Date : 2012-06-06 eCollection Date: 2012-01-01 DOI: 10.1186/1755-1536-5-S1-S22

Borna Mehrad, Robert M Strieter

引用次数: 20

Progression of renal fibrosis: the underestimated role of endothelial alterations. 肾纤维化的进展:内皮改变的低估作用。

Fibrogenesis & Tissue Repair Pub Date : 2012-06-06 eCollection Date: 2012-01-01 DOI: 10.1186/1755-1536-5-S1-S15

Dominique Guerrot, Jean-Claude Dussaule, Panagiotis Kavvadas, Jean-Jacques Boffa, Christos E Chadjichristos, Christos Chatziantoniou

{"title":"Progression of renal fibrosis: the underestimated role of endothelial alterations.","authors":"Dominique Guerrot, Jean-Claude Dussaule, Panagiotis Kavvadas, Jean-Jacques Boffa, Christos E Chadjichristos, Christos Chatziantoniou","doi":"10.1186/1755-1536-5-S1-S15","DOIUrl":"https://doi.org/10.1186/1755-1536-5-S1-S15","url":null,"abstract":"The vasculature of the kidney is a heterogeneous structure, whose functional integrity is essential for the regulation of renal function. Owing to the importance of the endothelium in vascular biology, chronic endothelial alterations are therefore susceptible to impair multiple aspects of renal physiology and, in turn, to contribute to renal fibrosis. Although systemic endothelial dysfunction is undoubtedly associated with chronic kidney disease, the role of the renal endothelium in the initiation and the progression of renal fibrosis remains largely elusive. In this article, we critically review recent evidence supporting direct and indirect contributions of renal endothelial alterations to fibrosis in the kidney. Specifically, the potential implications of renal endothelial dysfunction and endothelial paucity in parenchymal hypoxia, in the regulation of local inflammation, and in the generation of renal mesenchymal cells are reviewed. We thereafter discuss therapeutic perspectives targeting renal endothelial alterations during the initiation and the progression of renal fibrogenesis. ","PeriodicalId":12264,"journal":{"name":"Fibrogenesis & Tissue Repair","volume":"5 Suppl 1","pages":"S15"},"PeriodicalIF":0.0,"publicationDate":"2012-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1755-1536-5-S1-S15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31139558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 54

Molecular targets for therapy in systemic sclerosis. 系统性硬化症治疗的分子靶点。

Fibrogenesis & Tissue Repair Pub Date : 2012-06-06 eCollection Date: 2012-01-01 DOI: 10.1186/1755-1536-5-S1-S19

Naoki Iwamoto, Oliver Distler

{"title":"Molecular targets for therapy in systemic sclerosis.","authors":"Naoki Iwamoto, Oliver Distler","doi":"10.1186/1755-1536-5-S1-S19","DOIUrl":"https://doi.org/10.1186/1755-1536-5-S1-S19","url":null,"abstract":"Despite significant advances have been made in the recent years regarding organ-specific therapies, there is no approved 'disease-modifying' antifibrotic drug for systemic sclerosis (SSc) available to date. Although non-selective immunosuppressive agents are routinely used to treat patients with SSc, large well-controlled studies are lacking for almost all immunosuppressive agents and further evidence is required for long-term beneficial effects of these drugs. Considering these facts about immunosuppressive agents in SSc and also considering the high mortality of SSc, other therapeutic strategies are urgently needed. Recently an important role of the 5-hydroxytryptamine (5-HT: serotonin) pathway in fibrosis was reported. In this review, we discuss the role of 5-HT in fibrosis and therapeutic potential of this molecule. Besides 5-HT, there are a number of promising targets that have been extensively characterized in recent years. For many of these molecular targets, modifiers are readily available for clinical studies, and often these modifiers are used already in clinical use for other diseases. Results from these studies will show, in how far the promising preclinical results for novel antifibrotic strategies can be translated to clinical practice. ","PeriodicalId":12264,"journal":{"name":"Fibrogenesis & Tissue Repair","volume":"5 Suppl 1","pages":"S19"},"PeriodicalIF":0.0,"publicationDate":"2012-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1755-1536-5-S1-S19","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31139571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Fibroproliferative disorders: from biochemical analysis to targeted therapies Frauenchiemsee, Germany. 25-30 September 2010. Abstracts. 纤维增生性疾病:从生化分析到靶向治疗，德国Frauenchiemsee, 2010年9月25-30日。摘要。

Fibrogenesis & Tissue Repair Pub Date : 2012-06-06 DOI: 10.1186/1755-1536-5-s1-s1

引用次数: 3

Aberrant innate immune sensing leads to the rapid progression of idiopathic pulmonary fibrosis. 先天免疫感知异常导致特发性肺纤维化的快速进展。

Fibrogenesis & Tissue Repair Pub Date : 2012-06-06 eCollection Date: 2012-01-01 DOI: 10.1186/1755-1536-5-S1-S3

Cory M Hogaboam, Glenda Trujillo, Fernando J Martinez

{"title":"Aberrant innate immune sensing leads to the rapid progression of idiopathic pulmonary fibrosis.","authors":"Cory M Hogaboam, Glenda Trujillo, Fernando J Martinez","doi":"10.1186/1755-1536-5-S1-S3","DOIUrl":"https://doi.org/10.1186/1755-1536-5-S1-S3","url":null,"abstract":"Novel approaches are needed to define subgroups of patients with Idiopathic pulmonary fibrosis (IPF) at risk for acute exacerbations and/or accelerated progression of this generally fatal disease. Progression of disease is an integral component of IPF with a median survival of 3 to 5 years. Conversely, a high degree of variability in disease progression has been reported among series. The characteristics of patients at risk of earlier death predominantly rely on baseline HRCT appearance, but this concept that has been challenged. Disparate physiological approaches have also been taken to identify patients at risk of mortality, with varying results. We hypothesized that the rapid decline in lung function in IPF may be a consequence of an abnormal host response to pathogen-associated molecular patterns (PAMPs), leading to aberrant activation in fibroblasts and fibrosis. Analysis of upper and lower lobe surgical lung biopsies (SLBs) indicated that TLR9, a hypomethylated CpG DNA receptor, is prominently expressed at the transcript and protein level, most notably in biopsies from rapidly progressive IPF patients. Surprisingly, fibroblasts appeared to be a major cellular source of TLR9 expression in IPF biopsies from this group of progressors. Further, CpG DNA promoted profibrotic cytokine and chemokine synthesis in isolated human IPF fibroblasts, most markedly again in cells from patients with the rapidly progressive IPF phenotype, in a TLR9-dependent manner. Finally, CpG DNA exacerbated fibrosis in an in vivo model initiated by the adoptive transfer of primary fibroblasts derived from patients who exhibited rapidly progressing fibrosis. Together, these data suggested that TLR9 activation via hypomethylated DNA might be an important mechanism in promoting fibrosis particularly in patients prone to rapidly progressing IPF. ","PeriodicalId":12264,"journal":{"name":"Fibrogenesis & Tissue Repair","volume":"5 Suppl 1","pages":"S3"},"PeriodicalIF":0.0,"publicationDate":"2012-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1755-1536-5-S1-S3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31139354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 19

Inhibition of collagen fibril formation. 抑制胶原纤维的形成。

Fibrogenesis & Tissue Repair Pub Date : 2012-06-06 eCollection Date: 2012-01-01 DOI: 10.1186/1755-1536-5-S1-S29

Andrzej Steplewski, Andrzej Fertala

引用次数: 24

Employment of gene expression profiling to identify transcriptional regulators of hepatic stellate cells. 利用基因表达谱鉴定肝星状细胞的转录调节因子。

Fibrogenesis & Tissue Repair Pub Date : 2012-06-06 eCollection Date: 2012-01-01 DOI: 10.1186/1755-1536-5-S1-S12

Hideaki Shimada, Lakshman E Rajagopalan

引用次数: 7

Fibrosis in systemic sclerosis: common and unique pathobiology. 系统性硬化症纤维化:常见和独特的病理生物学。

Fibrogenesis & Tissue Repair Pub Date : 2012-06-06 eCollection Date: 2012-01-01 DOI: 10.1186/1755-1536-5-S1-S18

Swati Bhattacharyya, Jun Wei, Warren G Tourtellotte, Monique Hinchcliff, Cara G Gottardi, John Varga

{"title":"Fibrosis in systemic sclerosis: common and unique pathobiology.","authors":"Swati Bhattacharyya, Jun Wei, Warren G Tourtellotte, Monique Hinchcliff, Cara G Gottardi, John Varga","doi":"10.1186/1755-1536-5-S1-S18","DOIUrl":"https://doi.org/10.1186/1755-1536-5-S1-S18","url":null,"abstract":"Fibrosis in systemic sclerosis (SSc), a complex polygenic disease associated with autoimmunity and proliferative/obliterative vasculopathy, shares pathobiologic features in common with other fibrosing illnesses, but also has distinguishing characteristics. Fibroblast activation induced by transforming growth factor-β (TGF-β), Wnts and innate immune receptors, along with oxidative stress and reactive oxygen species (ROS) are implicated in pathogenesis. On the other hand, the roles of endothelial-mesenchymal differentiation and bone marrow-derived fibrocytes remain to be established. Fibrotic responses are modulated by transcriptional activators and cofactors, epigenetic factors, and microRNAs that can amplify or inhibit ligand-induced signaling. The nuclear orphan receptor PPAR-γ appears to be important in governing the duration and intensity of fibroblast activation and mesenchymal progenitor cell differentiation, and defects in PPAR-γ expression or function in SSc may underlie the uncontrolled progression of fibrosis. Identifying the perturbations in signaling pathways and cellular differentiation programs responsible for tissue damage and fibrosis in SSc allows their selective targeting using novel compounds, or by innovative uses of already-approved drugs (drug repurposing). ","PeriodicalId":12264,"journal":{"name":"Fibrogenesis & Tissue Repair","volume":"5 Suppl 1","pages":"S18"},"PeriodicalIF":0.0,"publicationDate":"2012-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1755-1536-5-S1-S18","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31136423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 37