Kruppel-like factor 5 is required for perinatal lung morphogenesis and function.
Kruppel-like factor 5 is required for perinatal lung morphogenesis and function.
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DOI：
10.1242/dev.021964
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发表时间：
2008-08
期刊：
影响因子：
--
通讯作者：
Whitsett JA
中科院分区：
文献类型：
--
作者：
Wan H;Luo F;Wert SE;Zhang L;Xu Y;Ikegami M;Maeda Y;Bell SM;Whitsett JA
出生后过渡到空气呼吸需要肺的解剖和生化成熟。肺的形态发生是由呼吸道上皮细胞和间充质细胞之间复杂的旁分泌相互作用所介导的，这些相互作用指导转录程序指导肺的图案化和细胞分化。在本研究中，建立了在胎肺呼吸道上皮细胞中条件缺失Kruppel样因子5基因(KLF5)的转基因小鼠。在囊状发育阶段，缺乏KLF5抑制了肺的成熟。KLF5Δ/Δ小鼠出生后立即死于呼吸窘迫。肺成熟和形态发生异常见于呼吸道上皮、细支气管壁和肺血管。传导和外周呼吸道的呼吸道上皮细胞均未成熟。表面活性物质磷脂减少，表面活性物质的储存形式--板层小体少见。基因芯片分析表明，KLF5影响调节表面活性物质脂质和蛋白质动态平衡、血管生成(包括Vegfa)和平滑肌细胞分化的基因表达。KLF5调节肺形态发生过程中控制旁分泌相互作用的基因，以及那些调节出生后肺功能所需的呼吸上皮成熟的基因。
The transition to air breathing after birth requires both anatomic and biochemical maturation of the lung. Lung morphogenesis is mediated by complex paracrine interactions between respiratory epithelial cells and mesenchymal cells that direct transcriptional programs guiding patterning and cytodifferentiation of the lung. In the present study, transgenic mice were generated in which the Kruppel-like factor 5 gene (Klf5) was conditionally deleted in respiratory epithelial cells in the fetal lung. Lack of KLF5 inhibited maturation of the lung during the saccular stage of development. Klf5Δ/Δ mice died of respiratory distress immediately after birth. Abnormalities in lung maturation and morphogenesis were observed in the respiratory epithelium, the bronchiolar smooth muscle, and the pulmonary vasculature. Respiratory epithelial cells of both the conducting and peripheral airways were immature. Surfactant phospholipids were decreased and lamellar bodies, the storage form of surfactant, were rarely found. mRNA microarray analysis demonstrated that KLF5 influenced the expression of genes regulating surfactant lipid and protein homeostasis, vasculogenesis, including Vegfa, and smooth muscle cell differentiation. KLF5 regulates genes controlling paracrine interactions during lung morphogenesis, as well as those regulating the maturation of the respiratory epithelium that is required for lung function after birth.
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影响因子：
2.6
作者：
Ding, H;Wu, XL;Nagy, A
通讯作者：
Nagy, A
影响因子：
4.6
作者：
Bell, Sheila M.;Schreiner, Claire M.;Whitsett, Jeffrey A.
通讯作者：
Whitsett, Jeffrey A.
DOI：
10.1073/pnas.0604946103
发表时间：
2006-08-01
影响因子：
11.1
作者：
Chen, Xueni;Hyatt, Brian A.;Shannon, John M.
通讯作者：
Shannon, John M.
影响因子：
2.5
作者：
Moore-Scott, Billie A.;Opoka, Robert;Wells, James M.
通讯作者：
Wells, James M.
影响因子：
4.6
作者：
Martis, PC;Whitsett, JA;Ikegami, M
通讯作者：
Ikegami, M