Transforming growth factor-beta signaling across ages: from distorted lung development to chronic obstructive pulmonary disease.
Transforming growth factor-beta signaling across ages: from distorted lung development to chronic obstructive pulmonary disease.
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DOI：
10.1513/pats.200908-087rm
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发表时间：
2009-12-01
期刊：
影响因子：
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通讯作者：
Eickelberg, Oliver
中科院分区：
文献类型：
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作者：
Morty, Rory E;Konigshoff, Melanie;Eickelberg, Oliver
分泌生长因子的转化生长因子（TGF）-β超家族由40多个成员组成，包括TGF-β同种型本身、骨形态发生蛋白和激活素。这些因素中的大多数已被证明对正常器官发育至关重要，这一过程经常在慢性疾病中重演。重要的是，TGF-β超家族成员是肺中细胞外基质组成和肺泡上皮细胞和成纤维细胞功能的关键调节剂。因此，在肺发育和疾病期间，TGF-β通过提供生理上皮细胞功能和适当气体交换所需的结构要求和功能微环境来控制肺稳态。TGF-β信号传导的长期改变已被证明会导致肺的结构变化，损害气体交换和肺功能，如在肺发育停滞中所见，这是支气管肺发育不良、肺纤维化和慢性阻塞性肺病的特征。所有这些综合征都有功能性肺泡结构的丧失，最终导致预期寿命缩短。在这篇综述中，我们涵盖了我们目前对TGF-β信号传导对慢性肺部疾病的影响的理解。我们专注于支气管肺发育不良和慢性阻塞性肺疾病中扭曲的TGF-β信号传导，分别作为早产儿和成熟肺的原型疾病，其特征均为肺泡单位的功能和结构损失。
The transforming growth factor (TGF)-beta superfamily of secreted growth factors consists of more than 40 members, including the TGF-beta isoforms themselves, bone morphogenetic proteins, and activins. Most of these factors have been shown to be essential for proper organ development, a process often recapitulated in chronic diseases. Importantly, TGF-beta superfamily members are key regulators of extracellular matrix composition and alveolar epithelial cell and fibroblast function in the lung. Both during lung development and disease, TGF-betas therefore control lung homeostasis by providing the structural requirements and functional micromilieu needed for physiological epithelial cell function and proper gas exchange. Prolonged alterations of TGF-beta signaling have been shown to result in structural changes in the lung that compromise gas exchange and lung function, as seen in arrested lung development, a feature of bronchopulmonary dysplasia, lung fibrosis, and chronic obstructive pulmonary disease. All these syndromes share a loss of functional alveolar structures, which ultimately leads to a decreased life expectancy. In this review, we cover our current understanding of the impact of TGF-beta signaling on chronic lung disease. We focus on distorted TGF-beta signaling in bronchopulmonary dysplasia and chronic obstructive pulmonary disease as prototype diseases of the premature and matured lung, respectively, which are both characterized by functional and structural loss of alveolar units.