Contributions of retinoids to the generation and repair of the pulmonary alveolus
Contributions of retinoids to the generation and repair of the pulmonary alveolus
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DOI：
10.1378/chest.121.5_suppl.206s
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发表时间：
2002-05-01
期刊：
影响因子：
9.6
通讯作者：
McGowan, SE
中科院分区：
文献类型：
--
作者：
McGowan, SE
COPD与肺功能的进行性、不可逆下降相关。这在很大程度上是由肺气肿、肺泡的持续炎性破坏和增加的空气空间大小、肺弹性回缩的损失和过度充气引起的。发现新的药物，可以减少肺破坏和气流限制的速度，甚至停止或逆转潜在的过程仍然是治疗这种疾病的“圣杯”。最近的报告表明，维甲酸显着改善大鼠的弹性蛋白酶诱导的肺气肿引起了相当大的兴趣，类维生素A和其他肺泡形态作为潜在的治疗药物。本文综述了哺乳动物肺泡形成的机制，主要发生在出生后。本文就内源性维甲酸在肺结构细胞（上皮细胞和间充质细胞）分化和肺发育中的作用进行了讨论。还讨论了肺的发育和结构的研究，在小鼠的基因改变方面的亚型维甲酸受体的表达。类维生素A和其他生长因子对弹性蛋白基因表达和肺泡形成的影响，以及作为治疗剂干扰这些过程的药物的潜在缺陷。
COPD is associated with a progressive, irreversible decline in pulmonary function. This is caused in large part by emphysema, the ongoing inflammatory destruction of the alveoli and increased airspace size, loss of lung elastic recoil, and hyperinflation. The discovery of novel drugs that can reduce the rate of lung destruction and airflow limitation, or even stop or reverse the underlying processes remains a "holy grail" for the therapy of this disorder. Recent reports that retinoic acid markedly ameliorates the emphysema induced in rats by administration of elastase have sparked considerable interest in retinoids and other alveolar morphogens as potential therapeutic agents. This review focuses on mechanisms involved in mammalian alveolar formation, which occurs mainly after birth. Roles of endogenous retinoids on pulmonary structural cell (epithelial and mesenchymal cells) differentiation and lung development re discussed. Also discussed are lung development and structural studies in mice that are genetically altered with respect to the expression of subtypes of retinoid receptors. Effects of retinoids and other growth factors on elastin gene expression and alveolus formation, and the potential pitfalls of drugs that interfere with these processes as therapeutic agents are addressed.