Expression Of Interrelated Polypeptides And Their Regulative Function In Type Ⅱ Alveolar Cells Of Fetal Lungs

Objective: In this work, distributions of the interrelated proteins: the fibroblast growth factor receptor (FGFR), bone morphogenetic protein-4 (BMP-4), rasp21 protein , thyroid transcription factor-1(TTF-1) and surface protein-b(SP-B) in human fetal lung were determined, their important function properties in regulating lung morphogenesis , differentiation and maturation were studied, as well as their relationships between each other.Methods: 15 specimens of human fetal lungs (from the 12thw to 35thw of gestation) were obtained. The expression of 5 kinds of polypeptides (FGFR, BMP-4, rasp21 protein, TTF-1, and SP-B) were examined by immunohistochemistry and re-stained by SP methods.Results: 1. It is showed that FGFR firstly localized in the airway surface epithelium during early lung (12thw ) development. Its staining in distal bronchiolar epithelial cells is always more intense than that of proximal epithelial cells. Its reaction reached the peak on fetal age 18th w. In this stage, the positive reactions were mainly detected in proximal and distal bronchiolar epithelial cells and also in type II alveolar cells. In 18thw, we can get the staining of BMP-4 in the airway surface epithelium, but its staining is more obvious in airway epithelium than that of type II alveolar cells. From 22nd w to 25th w, the expression of BMP-4 in distal bronchiolar epithelial cells and in type II alveolar cells has reinforced. In 16th w, rasp21 protein were expressed in proximal bronchioles but epithelial cells expressed at low levels. In 18thw, rasp21 protein were expressed throughout fetal lung development and showed at high levers. In 20thw, the intensity of rasp21 protein was expressed weakly except proximal bronchiolar epithelial cells. Furthermore, in the late stage of development, these threefactors all have no active reaction in the fetal lungs. 2. In 16thw, TTF-1 can be detected prominently in the nuclei of distal lung buds. With the development of fetal lungs, the staining of distal epithelial cells reinforced gradually. In the mid of development, TTF-1 located gradually in the newly-formed terminal cell of respiratory tract, meanwhile, several cell masses which located in the mesenchyme can be detected with the antibody of TTF-1. In the late of stage, they were slighter in the fetal lung and only apposition in the type II alveolar cells. The expression of SP-B was later than that of TTF-1 in lung. They were faint in the 18thw lung. With the development, the expression shifted gradually from proximal to distal epithelial cells, and the intensity is stronger than that of early stage. In 35thw, we only detected its expression in the cytoplasm of type II alveolar cells.Conclusion: The positive reactions of FGFR, BMP-4, rasp21 protein, TTF-1 and SP-B were respectively different during different stages, which suggests that their functions are changing at individual developmental periods. FGFR, BMP-4 and rasp21 protein mainly accelerate proliferation and differentiation of the type II alveolar cells, and make they more mature in morphology. TTF-1 and SP-B mainly make it mature in function and suitable in respiration. Normal development of fetal lung depends on these factors mutual coordination.