Insulin utilizes the PI 3-kinase pathway to inhibit SP-A gene expression in lung epithelial cells.
Insulin utilizes the PI 3-kinase pathway to inhibit SP-A gene expression in lung epithelial cells.
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DOI：
10.1186/rr191
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发表时间：
2002
影响因子：
5.8
通讯作者：
Snyder JM
中科院分区：
文献类型：
--
作者：
Miakotina OL;Goss KL;Snyder JM
有人提出，高胰岛素水平可能会导致糖尿病母亲的胎儿肺发育延迟。肺发育中的一个关键事件是产生足够量的肺表面活性物质。胰岛素抑制肺上皮细胞表面活性蛋白A（SP-A）的表达，SP-A是肺上皮细胞中主要的表面活性物质相关蛋白。在本研究中，我们研究了胰岛素抑制SP-A基因表达的信号转导途径。将H441细胞、人肺腺癌细胞系或人胎肺外植体与或不与胰岛素一起孵育。转录运行分析用于确定SP-A基因转录速率。采用北方印迹法检测不同信号转导抑制剂对SP-A基因表达的影响。免疫印迹分析用于评估信号转导蛋白激酶的水平和磷酸化状态。胰岛素在1小时内降低人肺上皮细胞SP-A基因转录。胰岛素不影响p44/42丝裂原活化蛋白激酶（MAPK）磷酸化，胰岛素对SP-A mRNA水平的抑制不受PD 98059（p44/42 MAPK通路抑制剂）的影响。相比之下，胰岛素在15分钟内增加p70 S6激酶Thr 389磷酸化。磷脂酰肌醇3-激酶（PI 3-kinase）抑制剂Wortmannin或LY 294002，或PI 3-kinase通路下游效应子p70 S6激酶激活抑制剂rapamycin，可消除或减弱胰岛素诱导的SP-A mRNA水平抑制。胰岛素抑制肺上皮细胞中SP-A基因表达可能通过雷帕霉素敏感的PI 3-激酶信号通路发生。
It has been proposed that high insulin levels may cause delayed lung development in the fetuses of diabetic mothers. A key event in lung development is the production of adequate amounts of pulmonary surfactant. Insulin inhibits the expression of surfactant protein A (SP-A), the major surfactant-associated protein, in lung epithelial cells. In the present study, we investigated the signal transduction pathways involved in insulin inhibition of SP-A gene expression. H441 cells, a human lung adenocarcinoma cell line, or human fetal lung explants were incubated with or without insulin. Transcription run-on assays were used to determine SP-A gene transcription rates. Northern blot analysis was used to examine the effect of various signal transduction inhibitors on SP-A gene expression. Immunoblot analysis was used to evaluate the levels and phosphorylation states of signal transduction protein kinases. Insulin decreased SP-A gene transcription in human lung epithelial cells within 1 hour. Insulin did not affect p44/42 mitogen-activated protein kinase (MAPK) phosphorylation and the insulin inhibition of SP-A mRNA levels was not affected by PD98059, an inhibitor of the p44/42 MAPK pathway. In contrast, insulin increased p70 S6 kinase Thr389 phosphorylation within 15 minutes. Wortmannin or LY294002, both inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase), or rapamycin, an inhibitor of the activation of p70 S6 kinase, a downstream effector in the PI 3-kinase pathway, abolished or attenuated the insulin-induced inhibition of SP-A mRNA levels. Insulin inhibition of SP-A gene expression in lung epithelial cells probably occurs via the rapamycin-sensitive PI 3-kinase signaling pathway.
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DOI：
10.1073/pnas.92.17.7686
发表时间：
1995-08-15
影响因子：
11.1
作者：
DUDLEY, DT;PANG, L;SALTIEL, AR
通讯作者：
SALTIEL, AR
影响因子：
2.8
作者：
DEGROOT, RP;BALLOU, LM;SASSONECORSI, P
通讯作者：
SASSONECORSI, P
DOI：
10.1016/0167-4889(88)90179-6
发表时间：
1988-06-30
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
OREILLY, MA;GAZDAR, AF;WHITSETT, JA
通讯作者：
WHITSETT, JA
影响因子：
11.4
作者：
PEARSON, RB;DENNIS, PB;THOMAS, G
通讯作者：
THOMAS, G
DOI：
10.1165/ajrcmb.18.2.2824
发表时间：
1998-02-01
影响因子：
6.4
作者：
Xu, XS;McCormick-Shannon, K;Mason, RJ
通讯作者：
Mason, RJ