Thyroid hormone drives fetal cardiomyocyte maturation
Thyroid hormone drives fetal cardiomyocyte maturation
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DOI：
10.1096/fj.10-179895
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发表时间：
2012-01-01
期刊：
影响因子：
4.8
通讯作者：
Thornburg, Kent L.
中科院分区：
文献类型：
--
作者：
Chattergoon, Natasha N.;Giraud, George D.;Thornburg, Kent L.
三碘- l -甲状腺原氨酸（T-3）在体外抑制近期血清刺激的胎羊心肌细胞增殖。因此，我们假设T-3是体内心肌细胞成熟的主要刺激物。我们研究了妊娠125-130天（足月145天）的三组羊胎儿：输注t -3组，以模拟胎儿足月水平（血浆t -3水平从0.1增加到1.0 ng/ml; t（1/2）类似于24小时）；甲状腺切除组，以产生低甲状腺激素水平；另一组为整车注射组，作为完整对照。妊娠130 d时，取左心室游离壁切片，酶解剩余心肌。测量左心室组织中参与细胞周期调节的蛋白（p21, cyclin D1），增殖（ERK）和肥厚（mTOR）。升高的T-3增加心肌细胞成熟率的证据包括宽度增加14%，双核增加31%，增殖减少39%，cyclin D1蛋白减少150%，p21蛋白增加500%。磷酸化- mtor、ANP和SERCA2a的表达增加也表明T-3促进了胎儿心肌细胞的成熟和肥厚。甲状腺切除的胎儿细胞周期活性和双核发育降低。这些发现支持了T-3是产前心肌细胞成熟的主要驱动因素的假设。-张晓明，张晓明，张晓明，张晓明。甲状腺激素对胎儿心肌细胞发育的影响[j] .中国生物医学工程学报，2014,33(4):559 - 567（2012）。www.fasebj.org
Tri-iodo-L-thyronine (T-3) suppresses the proliferation of near-term serum-stimulated fetal ovine cardiomyocytes in vitro. Thus, we hypothesized that T-3 is a major stimulant of cardiomyocyte maturation in vivo. We studied 3 groups of sheep fetuses on gestational days 125-130 (term similar to 145 d): a T-3-infusion group, to mimic fetal term levels (plasma T-3 levels increased from similar to 0.1 to similar to 1.0 ng/ml; t(1/2) similar to 24 h); a thyroidectomized group, to produce low thyroid hormone levels; and a vehicle-infusion group, to serve as intact controls. At 130 d of gestation, sections of left ventricular freewall were harvested, and the remaining myocardium was enzymatically dissociated. Proteins involved in cell cycle regulation (p21, cyclin D1), proliferation (ERK), and hypertrophy (mTOR) were measured in left ventricular tissue. Evidence that elevated T-3 augmented the maturation rate of cardiomyocytes included 14% increased width, 31% increase in binucleation, 39% reduction in proliferation, 150% reduction in cyclin D1 protein, and 500% increase in p21 protein. Increased expression of phospho-mTOR, ANP, and SERCA2a also suggests that T-3 promotes maturation and hypertrophy of fetal cardiomyocytes. Thyroidectomized fetuses had reduced cell cycle activity and binucleation. These findings support the hypothesis that T-3 is a prime driver of prenatal cardiomyocyte maturation.-Chattergoon, N. N., Giraud, G. D., Louey, S., Stork, P., Fowden, A. L., Thornburg, K. L. Thyroid hormone drives fetal cardiomyocyte maturation FASEB J. 26, 397-408 (2012). www.fasebj.org