Role of Growth Differentiation Factor 15 in Lung Disease and Senescence: Potential Role Across the Lifespan.
Role of Growth Differentiation Factor 15 in Lung Disease and Senescence: Potential Role Across the Lifespan.
复制标题
生长分化因子15在肺部疾病和衰老中的作用：整个生命周期的潜在作用。
DOI：
10.3389/fmed.2020.594137
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发表时间：
2020
影响因子：
3.9
通讯作者：
Lingappan K
中科院分区：
文献类型：
--
作者：
Al-Mudares F;Reddick S;Ren J;Venkatesh A;Zhao C;Lingappan K
生长分化因子15（Growth Differentiation Factor 15，GDF 15）是转化生长因子-β（transforming growth factor-β，TGF-β）超家族的一个分支，在正常生理条件下广泛表达。GDF 15表达在许多病理状态期间增加，并且作为细胞应激的标志物。GDF 15在病理条件下具有多种甚至矛盾的作用，因为其作用可能是剂量和时间依赖性的，并且基于靶组织和下游途径而变化。GDF 15已经成为作为衰老相关分泌表型的一部分的最公认的蛋白质之一。细胞衰老在从早产儿的支气管肺发育不良到老年人的COPD和特发性肺纤维化的许多肺部疾病中起着重要作用。据报道，GDF 15水平可作为慢性阻塞性肺疾病、肺纤维化和肺动脉高压的有用生物标志物，并可预测疾病严重程度、肺功能下降和死亡率。脑干中的胶质细胞系源性神经营养因子家族受体α样（GFRAL）已被鉴定为唯一经验证的GDF 15受体，并介导GDF 15介导的厌食和消瘦。GDF 15发挥其肺部作用的机制和途径正在阐明。基于循环水平的变化或通过GDF 15激活外周代谢变化的中枢作用，GDF 15也可能对肺产生影响。本文综述了GDF 15在不同肺部疾病中的作用及其在细胞衰老中的作用。
Growth Differentiation Factor 15 (GDF15) is a divergent member of transforming growth factor-beta (TGF-β) superfamily and is ubiquitously expressed, under normal physiological conditions. GDF15 expression increases during many pathological states and serves a marker of cellular stress. GDF15 has multiple and even paradoxical roles within a pathological condition, as its effects can be dose- and time-dependent and vary based on the targeted tissues and downstream pathways. GDF15 has emerged as one of the most recognized proteins as part of the senescence associated secretory phenotype. Cellular senescence plays a major role in many lung diseases across the life-span from bronchopulmonary dysplasia in the premature neonate to COPD and idiopathic pulmonary fibrosis in aged adults. GDF15 levels have been reported to be as a useful biomarker in chronic obstructive pulmonary disease, lung fibrosis and pulmonary arterial hypertension and predict disease severity, decline in lung function and mortality. Glial-cell-line-derived neurotrophic factor family receptor alpha-like (GFRAL) in the brain stem has been identified as the only validated GDF15 receptor and mediates GDF15-mediated anorexia and wasting. The mechanisms and pathways by which GDF15 exerts its pulmonary effects are being elucidated. GDF15 may also have an impact on the lung based on the changes in circulating levels or through the central action of GDF15 activating peripheral metabolic changes. This review focuses on the role of GDF15 in different lung diseases across the lifespan and its role in cellular senescence.
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