Leptin promotes fetal lung maturity and upregulates SP-A expression in pulmonary alveoli type-II epithelial cells involving TTF-1 activation.
Leptin promotes fetal lung maturity and upregulates SP-A expression in pulmonary alveoli type-II epithelial cells involving TTF-1 activation.
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瘦素促进胎儿肺成熟并上调参与 TTF-1 激活的 II 型肺泡上皮细胞中 SP-A 的表达
DOI：
10.1371/journal.pone.0069297
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Cai WB
中科院分区：
文献类型：
--
作者：
Chen H;Zhang JP;Huang H;Wang ZH;Cheng R;Cai WB
胎盘激素瘦素在胎儿和新生儿生长中具有重要作用，并可预防瘦素缺乏小鼠的呼吸抑制。研究了瘦素对低出生体重儿和早产儿呼吸窘迫的影响。然而，瘦素如何促进胎儿肺成熟和改善新生儿呼吸窘迫尚不清楚。在本研究中，我们发现在胎儿生长受限（FGR）大鼠模型中，产前用瘦素治疗2 d可显著增加相对肺泡面积并改善胎儿肺的成熟度。瘦素治疗组的平均出生体重和肺湿重高于pbs治疗组，表明促进了胎儿的生长。瘦素在体内和体外上调ii型肺泡上皮细胞（AECs）表面活性剂蛋白（SP） A的胞内表达和胞外分泌。瘦素对甲状腺转录因子-1 （TTF-1）的蛋白表达和转录活性有双重积极作用，TTF-1是ii型aec中肺分支形态发生和SP-A表达所必需的核转录因子。通过RNA干扰敲低TTF-1表明TTF-1可能在瘦素诱导的SP-A表达中起重要作用。这些结果提示瘦素在治疗FGR方面可能具有很大的治疗潜力，并且瘦素介导的SP-A诱导和胎儿肺成熟度依赖于TTF-1。
The placental hormone leptin has important functions in fetal and neonatal growth, and prevents depressed respiration in leptin-deficient mice. The effect of leptin on respiratory distress suffered by low birth weight and premature infants has been studied. However, it is unclear how leptin enhances lung maturity in the fetus and ameliorates neonatal respiratory distress. In the present study, we found that antenatal treatment with leptin for 2 d significantly enhanced the relative alveolus area and improved the maturity of fetal lungs in a rat model of fetal growth restriction (FGR). Mean birth weight and lung wet weight were higher in the leptin-treated group than in the PBS-treated group, indicating promotion of fetal growth. Leptin upregulated the intracellular expression and extracellular secretion of surfactant protein (SP) A in type-II alveolar epithelial cells (AECs) in vivo and in vitro. Dual positive effects of leptin were found on protein expression and transcriptional activity of thyroid transcription factor-1 (TTF-1), a nuclear transcription essential for branching morphogenesis of the lung and expression of SP-A in type-II AECs. Knockdown of TTF-1 by RNA interference indicated that TTF-1 may play a vital role in leptin-induced SP-A expression. These results suggest that leptin may have great therapeutic potential for the treatment of FGR, and leptin-mediated SP-A induction and lung maturity of the fetus are TTF-1 dependent.
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影响因子：
8
作者：
Hassink, SG;deLancey, E;Funanage, VL
通讯作者：
Funanage, VL
影响因子：
3.1
作者：
Lipsett, Jill;Tamblyn, Michelle;Owens, Julie A.
通讯作者：
Owens, Julie A.
影响因子：
3.6
作者：
Kirwin, Susan M.;Bhandari, Vineet;Funanage, Vicky L.
通讯作者：
Funanage, Vicky L.
DOI：
10.1016/0002-9378(95)90222-8
发表时间：
1995-07-01
影响因子：
9.8
作者：
CROWLEY, PA
通讯作者：
CROWLEY, PA
DOI：
10.1073/pnas.260501697
发表时间：
2000-12-19
影响因子：
11.1
作者：
Ahlbom, E;Gogvadze, V;Ceccatelli, S
通讯作者：
Ceccatelli, S