Chen M F, Gray K D, Prentice M A, Mariano J M, Jakowlew S B
Department of Pathology, McGill University, Montreal, Canada.
Pediatr Res. 1999 Jul;46(1):61-70. doi: 10.1203/00006450-199907000-00011.
Pulmonary hypoplasia has been found in the human neonatal autopsy population and has been attributed to an alteration in epithelial-mesenchymal interactions during development of the lung. Pulmonary acinar aplasia is a very rare and severe form of pulmonary hypoplasia. The transforming growth factor-betas (TGF-beta) are multifunctional regulatory peptides that are secreted by a variety of normal and malignant cells and are expressed in developing organs including the lung; their tissue distribution patterns have possible significance for signaling roles in many epithelial-mesenchymal interactions. Here, we report our examination of TGF-beta in the lungs of a term female infant diagnosed with pulmonary acinar aplasia whose autopsy revealed extremely hypoplastic lungs with complete absence of alveolar ducts and alveoli. Immunohistochemical and in situ hybridization analyses were used to localize and measure the proteins and mRNA, respectively, for TGF-beta1, TGF-beta2, TGF-beta3, and TGF-beta type I and type II receptors (TGF-beta RI and RII) in formalin-fixed and paraffin-embedded sections of these hypoplastic lungs and normal lungs. Immunostaining for TGF-beta1, TGF-beta2, and TGF-beta RI and RII was significantly lower in the bronchial epithelium and muscle of the hypoplastic lungs than in normal lungs, whereas no difference was detected in staining for other proteins including Clara cell 10-kD protein, adrenomedullin, hepatocyte growth factor/scatter factor, and hepatocyte growth factor receptor/Met in the hypoplastic and normal lungs or in the liver and kidneys of this infant compared with normal liver and kidney. In addition, in situ hybridization showed that TGF-beta1 and TGF-beta RI transcripts were considerably reduced in the bronchial epithelium of the hypoplastic lung compared with normal lung. These results show that there is a selective reduction of TGF-beta in pulmonary acinar aplasia and suggest that the signaling action of TGF-beta in epithelial-mesenchymal interactions in the lungs of this developmental condition may be compromised.
在人类新生儿尸检群体中发现了肺发育不全，其原因被认为是肺发育过程中上皮 - 间充质相互作用发生改变。肺腺泡发育不全是一种非常罕见且严重的肺发育不全形式。转化生长因子 -β（TGF -β）是多功能调节肽，由多种正常和恶性细胞分泌，并在包括肺在内的发育器官中表达；它们的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。在此，我们报告了对一名足月女婴肺部TGF -β的检查，该女婴被诊断为肺腺泡发育不全，尸检显示肺部极度发育不全，完全没有肺泡管和肺泡。免疫组织化学和原位杂交分析分别用于在这些发育不全肺和正常肺的福尔马林固定石蜡包埋切片中定位和测量TGF -β1、TGF -β2、TGF -β3以及TGF -βⅠ型和Ⅱ型受体（TGF -β RI和RII）的蛋白质和mRNA。发育不全肺的支气管上皮和肌肉中TGF -β1、TGF -β2以及TGF -β RI和RII的免疫染色明显低于正常肺，而在发育不全肺和正常肺中，包括克拉拉细胞10 - kD蛋白、肾上腺髓质素、肝细胞生长因子/分散因子以及肝细胞生长因子受体/Met等其他蛋白质的染色，与该婴儿的正常肝脏和肾脏相比，在发育不全肺和正常肺以及肝脏和肾脏中均未检测到差异。此外，原位杂交显示，与正常肺相比，发育不全肺的支气管上皮中TGF -β1和TGF -β RI转录本显著减少。这些结果表明，肺腺泡发育不全中TGF -β存在选择性减少，提示在这种发育状况下，TGF -β在肺上皮 - 间充质相互作用中的信号传导作用可能受到损害。
