PPARγ Signaling Mediates the Evolution, Development, Homeostasis, and Repair of the Lung.
PPARγ Signaling Mediates the Evolution, Development, Homeostasis, and Repair of the Lung.
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DOI：
10.1155/2012/289867
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发表时间：
2012
期刊：
影响因子：
2.9
通讯作者：
Torday JS
中科院分区：
文献类型：
--
作者：
Rehan VK;Torday JS
由可溶性生长因子介导的上皮 - 间充质相互作用决定了脊椎动物肺生理学的演变，包括发育、内稳态和修复。肺的所有这些积极适应性特性的最终共同途径是上皮甲状旁腺激素相关蛋白的表达，及其与间充质上其受体的结合，诱导脂肪成纤维细胞表达过氧化物酶体增殖物激活受体γ（PPARγ）。脂肪成纤维细胞随后产生瘦素，瘦素与肺泡Ⅱ型细胞结合，刺激其产生表面活性物质，这对于从鱼类到人类对大气氧的进化和生理适应都是必需的。各种各样的分子损伤破坏了这种高度进化的生理细胞 - 细胞相互作用，从过度扩张到氧化剂、感染和尼古丁，所有这些都可预见地导致间充质PPARγ表达缺失以及脂肪成纤维细胞转分化为肌成纤维细胞，肌成纤维细胞是肺纤维化的标志性细胞类型。通过利用这种深层的细胞 - 分子功能同源性作为调节肺内稳态的靶点，我们发现我们能够有效预防和/或逆转这些致病因素的有害影响，证明了进化生物学在预防和治疗慢性肺部疾病中的实用性。通过将健康和疾病的机制理解为一个进化连续体而非分离的过程，我们能够发展预测医学。
Epithelial-mesenchymal interactions mediated by soluble growth factors determine the evolution of vertebrate lung physiology, including development, homeostasis, and repair. The final common pathway for all of these positively adaptive properties of the lung is the expression of epithelial parathyroid-hormone-related protein, and its binding to its receptor on the mesenchyme, inducing PPARγ expression by lipofibroblasts. Lipofibroblasts then produce leptin, which binds to alveolar type II cells, stimulating their production of surfactant, which is necessary for both evolutionary and physiologic adaptation to atmospheric oxygen from fish to man. A wide variety of molecular insults disrupt such highly evolved physiologic cell-cell interactions, ranging from overdistention to oxidants, infection, and nicotine, all of which predictably cause loss of mesenchymal peroxisome-proliferator-activated receptor gamma (PPARγ) expression and the transdifferentiation of lipofibroblasts to myofibroblasts, the signature cell type for lung fibrosis. By exploiting such deep cell-molecular functional homologies as targets for leveraging lung homeostasis, we have discovered that we can effectively prevent and/or reverse the deleterious effects of these pathogenic agents, demonstrating the utility of evolutionary biology for the prevention and treatment of chronic lung disease. By understanding mechanisms of health and disease as an evolutionary continuum rather than as dissociated processes, we can evolve predictive medicine.
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DOI：
10.1053/siny.2002.0129
发表时间：
2002-10-01
期刊：
Seminars in neonatology : SN
影响因子：
--
作者：
Attar, Mohammad Ali;Donn, Steven M
通讯作者：
Donn, Steven M
影响因子：
2.1
作者：
Glenny, Robb W.
通讯作者：
Glenny, Robb W.
影响因子：
4.8
作者：
Gao, J;Serrero, G
通讯作者：
Serrero, G
影响因子：
3.6
作者：
Jobe AH
通讯作者：
Jobe AH
影响因子：
3.8
作者：
Boros, LG;Torday, JS;Rehan, VK
通讯作者：
Rehan, VK