Fibrosis: From Basic Mechanisms to Targeted Therapies

 描述(由申请人提供)：请求支持由Robert Lafyatis、Paolo G.V.Martini、Dean Seppard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。会议将于2016年2月7日至11日在科罗拉多州的Keystone举行。纤维化是许多疾病的主要过程，也是更多疾病的终末期，经常导致器官衰竭。然而，导致纤维化的机制一直知之甚少，针对纤维化的现有治疗方法也很有限。越来越多的人将纤维化理解为一个由免疫系统协调、或由炎症或细胞应激激活的动态过程。肺、肾、皮肤、肝脏和肌肉的纤维化通常伴随着各种不同的刺激。在理解Th2细胞反应、细胞死亡、炎症体和内质网以及氧化应激方面的进展为了解这些刺激因素提供了新的见解。了解促纤维化细胞因子，如TGFb、IL-13和CTGF的调节和相互作用，有助于进一步了解纤维化过程。最近的研究表明，纤维化是由特定的祖细胞和靶组织内的驻留细胞介导的。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影响。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，机械性的理解很快就会出现 回答长期存在的纤维性和终末期疤痕疾病的临床挑战。 因此，本次会议解决了与NHLBI任务相关的一个重要的公共卫生挑战。具体地说，纤维化是大多数间质性肺部疾病的终末期和危及生命的并发症，影响到许多成年人和儿童。目前对纤维性肺病的治疗非常有限，因此它仍然是一个主要的国家健康问题。肺纤维化最常见的形式是特发性肺纤维化(IPF)，在美国的患病率在28/100,000到63/100,000之间，这取决于病例定义使用的是狭义标准还是更广泛的标准。目前的估计是，从确诊之日起，患者的平均生存期为3年。各种原因引起的肺纤维化的患病率可能是IPF患病率的3倍。

 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.