Buisine M P, Devisme L, Copin M C, Durand-Réville M, Gosselin B, Aubert J P, Porchet N
Unité INSERM U377, Lille, France.
Am J Respir Cell Mol Biol. 1999 Feb;20(2):209-18. doi: 10.1165/ajrcmb.20.2.3259.
The epithelial surface of the respiratory tract is coated with a protective film of mucus secreted by epithelial goblet and submucosal gland cells. Histology of the airway mucosa and composition of secretions during the second trimester of fetal life are known to differ from the normal adult in that these secretions show similarities with those of hypersecretory disorders. To provide information regarding cell-specific expression of mucin genes and their relation to developmental patterns of epithelial cytodifferentiation, we studied the expression of eight different mucin genes (MUC1-MUC4, MUC5AC, MUC5B, MUC6, MUC7) in human embryonic and fetal respiratory tract using in situ hybridization. These investigations demonstrated that MUC4 is the earliest gene expressed in the foregut at 6.5 wk, followed by MUC1 and MUC2 from 9. 5 wk of gestation in trachea, bronchi, epithelial tubules, and terminal sacs before epithelial cytodifferentiation. In contrast, MUC5AC, MUC5B, and MUC7 are expressed at later gestational ages concomitant with epithelial cytodifferentiation. During this developmental stage, MUC1 and MUC4 mRNAs are located in goblet and ciliated cells, whereas MUC2 mRNAs are located in basal and goblet cells. MUC5AC expression is confined to goblet cells. In the submucosal glands, MUC2 mRNAs are located in both mucous and serous cells, whereas MUC5B and MUC7 mRNAs are expressed in mucous and in serous cells, respectively. These data suggest distinct developmental roles for MUC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC7 in the elongation, branching, and epithelial cytodifferentiation of the respiratory tract during ontogenesis. Distinct patterns of mucin gene expression are also likely to play an important role in regulating appropriate epithelial cell proliferation and cytodifferentiation in adult airway mucosa as it is indicated by aberrant expression in hypersecretory disorders.
呼吸道的上皮表面覆盖着一层由上皮杯状细胞和黏膜下腺细胞分泌的黏液保护膜。已知胎儿生命中期气道黏膜的组织学和分泌物组成与正常成年人不同，因为这些分泌物与分泌过多性疾病的分泌物相似。为了提供有关黏蛋白基因的细胞特异性表达及其与上皮细胞分化发育模式的关系的信息，我们使用原位杂交技术研究了人类胚胎和胎儿呼吸道中八种不同黏蛋白基因（MUC1 - MUC4、MUC5AC、MUC5B、MUC6、MUC7）的表达。这些研究表明，MUC4是在前肠6.5周时最早表达的基因，随后在妊娠9.5周时，在气管、支气管、上皮小管和终末囊的上皮细胞分化之前，MUC1和MUC2开始表达。相比之下，MUC5AC、MUC5B和MUC7在妊娠后期伴随着上皮细胞分化而表达。在这个发育阶段，MUC1和MUC4 mRNA位于杯状细胞和纤毛细胞中，而MUC2 mRNA位于基底细胞和杯状细胞中。MUC5AC的表达局限于杯状细胞。在黏膜下腺中，MUC2 mRNA位于黏液细胞和浆液细胞中，而MUC5B和MUC7 mRNA分别在黏液细胞和浆液细胞中表达。这些数据表明，MUC1、MUC2、MUC4、MUC5AC、MUC5B和MUC7在个体发育过程中对呼吸道的伸长、分支和上皮细胞分化具有不同的发育作用。黏蛋白基因表达的不同模式也可能在调节成年气道黏膜中适当的上皮细胞增殖和细胞分化中起重要作用，这在分泌过多性疾病中的异常表达中得到了体现。
