Fibrosis: From Basic Mechanisms to Targeted Therapies

纤维化：从基本机制到靶向治疗

• 批准号: 9039836
• 负责人: DAVID L. WOODLAND
• 金额: $ 1.5万
• 依托单位: KEYSTONE SYMPOSIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9039836
• 关键词: Address; Adult; Affect; Alcohols; Animal Disease Models; Area; Biology; Burn injury; Cell Death; Cells; Cellular Stress; Child; Chronic Disease; Chronic Kidney Failure; Cicatrix; Cirrhosis; Clinical; Clinical Trials; Collaborations; Colorado; Complication; Contracture; Crohn' s disease; Development; Diagnosis; Disease; Event; Fibroblasts; Fibrosis; Functional disorder; Future; Gene Expression Regulation; Hamman-Rich syndrome; Healed; Health; Heart failure; High Prevalence; Immune system; Inflammation; Interleukin-13; Interstitial Lung Diseases; Intestines; Joints; Kidney; Kidney Diseases; Kidney Failure; Knowledge; Learning; Life; Light; Liver; Liver diseases; Lung diseases; Mediating; Medical; Methodology; Mission; Modality; Modeling; Morbidity - disease rate; Muscle; Muscular Dystrophies; Myocardial Infarction; National Heart, Lung, and Blood Institute; Organ; Organ failure; Outcome; Oxidative Stress; Patients; Pericytes; Pharmacologic Substance; Phenotype; Prevalence; Process; Public Health; Pulmonary Fibrosis; Regulation; Renal Glycosuria; Research; Research Personnel; Scientist; Signaling Protein; Skin; Speed; Staging; Stimulus; Systemic Lupus Erythematosus; Systemic Scleroderma; Th2 Cells; Therapeutic; Therapeutic Intervention; Time; Tissues; Translations; Viral; Work; clinical application; clinical practice; connective tissue growth factor; cytokine; end stage disease; healing; insight; interest; meetings; new technology; nonalcoholic steatohepatitis; novel strategies; novel therapeutics; posters; progenitor; response; standard of care; symposium; targeted treatment; therapeutic target

 DESCRIPTION (provided by applicant): Support is requested for a Keystone Symposia meeting entitled Fibrosis: From Basic Mechanisms to Targeted Therapies, organized by Robert Lafyatis, Paolo G.V. Martini, Dean Sheppard and Lucie Peduto. The meeting will be held in Keystone, Colorado from February 7-11, 2016. Fibrosis is the primary process of many diseases and the end-stage of many more, frequently leading to organ failure. However, the mechanisms leading to fibrosis have been poorly understood and available therapeutics targeting fibrosis limited. Increasingly, fibrosis is understood as a dynamic process that is orchestrated by the immune system, or activated by inflammation or cellular stress. Fibrosis of lung, kidney, skin, liver and muscle typically follow a variety of different stimuli. Advances in understanding Th2 cell responses, cell death, the inflammasome and ER and oxidative stresses provide new insights into such stimuli. Understanding the regulation of, and interaction between, profibrotic cytokines such as TGFb, IL-13, and CTGF are shedding additional light on fibrotic processes. Recent studies indicate that fibrosis is mediated by dedicated progenitor and resident cells within target tissues. Fibroblast and perivascular cell phenotype and differentiatio are regulated not only by cytokines, but also by matrix composition and stiffness. Advances in the treatment of idiopathic pulmonary fibrosis and systemic sclerosis herald many new anti-fibrotic therapies that will soon enter clinical trials. Thus, mechanistic understandings will soon answer the long-standing clinical challenges of fibrotic and end-stage scarring diseases. Thus, this meeting addresses an important public health challenge relevant to the NHLBI mission. Specifically, fibrosis is the end stage and life-threatening complication of most interstitial lung diseases, affecting many adults and children. Current treatments for fibrotic lun disease are extremely limited, so it continues to represent a major national health problem. The most common form of pulmonary fibrosis, Idiopathic Pulmonary Fibrosis (IPF), has a prevalence in the US of between 28 and 63/100,000 depending on whether narrow or more broad criteria are used for case definition. Current estimates are that the mean survival is 3 years from the time of diagnosis. The prevalence of pulmonary fibrosis from all causes is probably 3 times higher than the prevalence of IPF.

 描述（由申请人提供）：要求支持由Robert Lafyatis，Paolo G. V. Martini，Dean Sheppard和Lucie Peduto组织的题为纤维化：从基本机制到靶向治疗的Keystone研讨会会议。会议将于2016年2月7日至11日在科罗拉多的基斯通举行。纤维化是许多疾病的主要过程，也是许多疾病的终末期，经常导致器官衰竭。然而，导致纤维化的机制知之甚少，并且可用的靶向纤维化的治疗剂有限。纤维化越来越多地被理解为一个动态过程，由免疫系统协调，或由炎症或细胞应激激活。肺、肾、皮肤、肝和肌肉的纤维化通常遵循各种不同的刺激。在理解Th 2细胞反应、细胞死亡、炎性小体和ER以及氧化应激方面的进展为此类刺激提供了新的见解。了解促纤维化细胞因子如TGFb、IL-13和CTGF的调节和相互作用正在使纤维化过程更加清晰。最近的研究表明，纤维化是由靶组织内的专用祖细胞和驻留细胞介导的。成纤维细胞和血管周围细胞的表型和分化不仅受细胞因子的调节，还受基质成分和硬度的调节。特发性肺纤维化和系统性硬化症的治疗进展预示着许多新的抗纤维化疗法即将进入临床试验。因此，机械的理解将很快 解决纤维化和终末期疤痕疾病长期存在的临床挑战。 因此，本次会议讨论了与国家HLBI使命有关的一个重要的公共卫生挑战。具体而言，纤维化是大多数间质性肺病的终末期和危及生命的并发症，影响许多成人和儿童。目前纤维化肺病的治疗方法非常有限，因此它仍然是一个主要的国家健康问题。最常见的肺纤维化形式，特发性肺纤维化（IPF），在美国的患病率为28/100，000至63/100，000，这取决于病例定义使用的是狭义标准还是广义标准。目前的估计是，从诊断之日起，平均生存期为3年。全因肺纤维化的患病率可能是IPF患病率的3倍。