An Extensive Genetic Program Occurring during Postnatal Growth in Multiple Tissues
An Extensive Genetic Program Occurring during Postnatal Growth in Multiple Tissues
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DOI：
10.1210/en.2008-0868
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发表时间：
2009-04-01
期刊：
影响因子：
4.8
通讯作者：
Baron, Jeffrey
中科院分区：
文献类型：
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作者：
Finkielstain, Gabriela P.;Forcinito, Patricia;Baron, Jeffrey
哺乳动物的体细胞生长在出生后早期是迅速的，但随后在多个组织中减慢并最终停止。我们假设存在一种出生后基因表达程序，该程序在多种组织中是共同的，并负责这种协调生长减速。与这一假设相一致，微阵列分析确定了1600多个基因，这些基因在雄性小鼠的肾脏、肺和心脏中随年龄（1周与4周）协调调节，其中包括许多调节增殖的基因。作为例子，我们专注于三个生长促进基因，Igf 2，Mest和Peg 3，随着年龄的增长显着下调。原位杂交显示，表达发生在器官特异性的实质细胞，并建议随着年龄的增长，表达减少主要是由于每个细胞的表达减少，而不是表达细胞的数量减少。在雄性大鼠甲状腺功能减退和生长抑制（在0-5周龄时由丙基硫氧嘧啶诱导）期间，这些基因表达的下降减缓，表明表达的正常下降是由生长驱动的，而不是由年龄本身驱动的。我们的结论是，有一个广泛的遗传程序发生在出生后的生活。许多相关基因在多个器官中协调调节，包括许多调节细胞增殖的基因。至少其中一些基因本身明显受到生长的调节，这表明，在胚胎中，建立了一种基因表达模式，允许多种组织的快速体细胞生长，但在出生后的生活中，这种生长导致基因表达的负反馈变化，反过来减缓并最终停止体细胞生长，从而对成年人的身体大小施加了根本限制。（内分泌学150：1791-1800，2009）
Mammalian somatic growth is rapid in early postnatal life but then slows and eventually ceases in multiple tissues. We hypothesized that there exists a postnatal gene expression program that is common to multiple tissues and is responsible for this coordinate growth deceleration. Consistent with this hypothesis, microarray analysis identified more than 1600 genes that were regulated with age (1 vs. 4 wk) coordinately in kidney, lung, and heart of male mice, including many genes that regulate proliferation. As examples, we focused on three growth-promoting genes, Igf2, Mest, and Peg3, that were markedly down-regulated with age. In situ hybridization revealed that expression occurred in organ-specific parenchymal cells and suggested that the decreasing expression with age was due primarily to decreased expression per cell rather than a decreased number of expressing cells. The declining expression of these genes was slowed during hypothyroidism and growth inhibition (induced by propylthiouracil at 0-5 wk of age) in male rats, suggesting that the normal decline in expression is driven by growth rather than by age per se. We conclude that there exists an extensive genetic program occurring during postnatal life. Many of the involved genes are regulated coordinately in multiple organs, including many genes that regulate cell proliferation. At least some of these are themselves apparently regulated by growth, suggesting that, in the embryo, a gene expression pattern is established that allows for rapid somatic growth of multiple tissues, but then, during postnatal life, this growth leads to negative-feedback changes in gene expression that in turn slow and eventually halt somatic growth, thus imposing a fundamental limit on adult body size. (Endocrinology 150: 1791-1800, 2009)