Montuenga L M, Mariano J M, Prentice M A, Cuttitta F, Jakowlew S B
Department of Cell and Cancer Biology, National Cancer Institute, Medicine Branch, Rockville, Maryland 20850, USA.
Endocrinology. 1998 Sep;139(9):3946-57. doi: 10.1210/endo.139.9.6205.
Transforming growth factor-beta (TGFbeta) and adrenomedullin (AM) are multifunctional regulatory peptides that are secreted by a variety of normal and malignant cells. The TGFbetas are expressed in developing organs and adults, and their tissue distribution pattern has possible significance for signaling roles in many epithelial-mesenchymal interactions. AM is also expressed in a variety of embryonic and adult tissues. The present study reports a comparison of the patterns of expression of the proteins and messenger RNAs (mRNAs) for TGFbeta1 and AM in the developing mouse embryo. Immunohistochemical and in situ hybridization analyses were performed on formalin-fixed paraffin-embedded sections of developing embryonic mouse tissues using specific antibodies and complementary RNA probes for TGFbeta1 and AM. The early placenta, including the giant trophoblastic cells, showed high levels of staining and hybridization for TGFbeta1 and AM proteins and mRNAs. The heart was the first organ that showed expression of TGFbeta1 and AM during embryogenesis. The spatio-temporal patterns of expression of TGFbeta1 and AM in cardiovascular, neural, and skeletal-forming tissues as well as in the main embryonic internal organs showed striking similarities. The lung, kidney, and intestine, in which epithelial-mesenchymal interactions occur, showed similar patterns of TGFbeta1 and AM expression. These data show colocalization of TGFbeta1 and AM in specific cell types associated with several tissues in the developing mouse embryo. Additionally, RT-PCR amplification and Northern blot hybridization showed expression of TGFbeta1 and AM mRNAs in all embryonic and adult mouse and rat tissues examined. Our data show that the expression of TGFbeta1 and AM is regulated in a spatial and temporal manner such that overlapping patterns of expression of TGFbeta1 and AM occur in several tissues at the same stage of development and in the same cellular location in rodent embryogenesis.
转化生长因子-β（TGFβ）和肾上腺髓质素（AM）是由多种正常细胞和恶性细胞分泌的多功能调节肽。TGFβ在发育中的器官和成年个体中表达，其组织分布模式在许多上皮-间充质相互作用中的信号传导作用可能具有重要意义。AM也在多种胚胎和成年组织中表达。本研究报告了发育中的小鼠胚胎中TGFβ1和AM的蛋白质及信使核糖核酸（mRNA）表达模式的比较。使用针对TGFβ1和AM的特异性抗体和互补RNA探针，对发育中的胚胎小鼠组织的福尔马林固定石蜡包埋切片进行了免疫组织化学和原位杂交分析。早期胎盘，包括巨大滋养层细胞，显示出TGFβ1和AM蛋白质及mRNA的高水平染色和杂交。心脏是胚胎发育过程中第一个显示TGFβ1和AM表达的器官。TGFβ1和AM在心血管、神经和骨骼形成组织以及主要胚胎内脏器官中的时空表达模式显示出惊人的相似性。发生上皮-间充质相互作用的肺、肾和肠显示出类似的TGFβ1和AM表达模式。这些数据表明，在发育中的小鼠胚胎中，TGFβ1和AM在与几种组织相关的特定细胞类型中共定位。此外，逆转录-聚合酶链反应（RT-PCR）扩增和Northern印迹杂交显示，在所检测的所有胚胎和成年小鼠及大鼠组织中均有TGFβ1和AM mRNA的表达。我们的数据表明，TGFβ1和AM的表达在空间和时间上受到调节，使得在发育的同一阶段以及啮齿动物胚胎发生的相同细胞位置，TGFβ1和AM在几种组织中出现重叠的表达模式。
