Mesenchymal nuclear factor I B regulates cell proliferation and epithelial differentiation during lung maturation.
Mesenchymal nuclear factor I B regulates cell proliferation and epithelial differentiation during lung maturation.
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DOI：
10.1016/j.ydbio.2011.04.002
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发表时间：
2011-06-15
影响因子：
2.7
通讯作者：
Gronostajski RM
中科院分区：
文献类型：
--
作者：
Hsu YC;Osinski J;Campbell CE;Litwack ED;Wang D;Liu S;Bachurski CJ;Gronostajski RM
核因子I（NFI）转录因子家族由调节小鼠和人类多器官系统发育的四个基因（Nfia、Nfib、Nfic和Nfix）组成。Nfib在肺间充质和上皮中表达，缺乏Nfib的小鼠具有严重的肺成熟缺陷，并且在出生时死亡。在这里，我们继续分析Nfib−/−肺的表型，并表明Nfib特异性地在肺间充质中控制晚期上皮细胞和间充质细胞的增殖和分化。在E18.5时，Nfib−/−肺中的PCNA、BrdU、PHH 3和Ki 67阳性细胞比野生型肺中的更多，并且在上皮细胞和间充质细胞中均观察到增殖标记物表达的增加。所有肺细胞中Nfib的缺失降低了E18.5肺中肺泡上皮细胞（Aqp 5和Sftpc）、Clara细胞（Scgb 1a 1）和纤毛细胞（Foxj 1）的标志物的表达。为了测试Nfib在肺间充质中的特定作用，我们产生并分析了Nfib flox/flox，Dermo 1-Cre小鼠。仅在间充质中Nfib的丢失导致Aqp 5、Sftpc和Foxj 1表达降低，细胞增殖增加，以及与Nfib−/−小鼠中观察到的类似的囊状形成缺陷。相反，间质特异性Nfib丢失对气道Scgb 1a 1的表达没有影响。微阵列和QPCR分析表明，肺间质中Nfib的缺失影响与细胞外基质、细胞粘附和FGF信号传导相关的基因的表达，这些基因可能影响远端肺成熟。我们的数据表明，间充质NFIb通过多种途径调节间充质和上皮细胞增殖，并且间充质NFI-B介导的信号对于远端肺上皮的成熟至关重要。
The Nuclear factor I (NFI) transcription factor family consists of four genes (Nfia, Nfib, Nfic and Nfix) that regulate the development of multiple organ systems in mice and humans. Nfib is expressed in both lung mesenchyme and epithelium and mice lacking Nfib have severe lung maturation defects and die at birth. Here we continue our analysis of the phenotype of Nfib−/− lungs and show that Nfib specifically in lung mesenchyme controls late epithelial and mesenchymal cell proliferation and differentiation. There are more PCNA, BrdU, PHH3 and Ki67 positive cells in Nfib−/− lungs than in wild type lungs at E18.5 and this increase in proliferation marker expression is seen in both epithelial and mesenchymal cells. The loss of Nfib in all lung cells decreases the expression of markers for alveolar epithelial cells (Aqp5 & Sftpc), Clara cells (Scgb1a1) and ciliated cells (Foxj1) in E18.5 lungs. To test for a specific role of Nfib in lung mesenchyme we generated and analyzed Nfibflox/flox, Dermo1-Cre mice. Loss of Nfib only in mesenchyme results in decreased Aqp5, Sftpc and Foxj1 expression, increased cell proliferation, and a defect in sacculation similar to that seen in Nfib−/− mice. In contrast, mesenchyme specific loss of Nfib had no effect on the expression of Scgb1a1 in the airway. Microarray and QPCR analyses indicate that the loss of Nfib in lung mesenchyme affects the expression of genes associated with extracellular matrix, cell adhesion and FGF signaling which could affect distal lung maturation. Our data indicate that mesenchymal Nfib regulates both mesenchymal and epithelial cell proliferation through multiple pathways and that mesenchymal NFI-B-mediated signals are essential for the maturation of distal lung epithelium.
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影响因子：
5.5
作者：
Bird, Anthony D.;Tan, Kheng H.;Cole, Timothy J.
通讯作者：
Cole, Timothy J.
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
6.9
作者：
Degterev, A;Foster, JA
通讯作者：
Foster, JA
影响因子：
4
作者：
LIGGINS, GC
通讯作者：
LIGGINS, GC
DOI：
10.1152/ajplung.00221.2006
发表时间：
2007-03-01
影响因子：
4.9
作者：
Deimling, Julie;Thompson, Kate;Post, Martin
通讯作者：
Post, Martin