Expression Of Interrelated Polypeptides And Their Regulative Function In Mouse Fetal Lungs

OBJECTIVEThe development of the fetal lung involves precise and strict regulating mechanism.During the process of the morphogenesis and cell differentiation, embryonic lung cellsare influenced by kinds of polypeptides. But little information is available on how theydirectIy influence lung morphogenesis and differentiation and on how they interact on inthe developing lung. In this work, distributions of the interrelated proteins: theepidermal growth factor receptor(EGFR), transforming groWth factor-9l, 62, 63(TGF-p l,pz, ps) and thyroid transcription factor- l (TTF-l ) in fetal and postnatal mouse Iungs weredetermined, their important function properties in regulating lung morphogenesis,differentiation and maturation were studied, and their reIationships between each otherwere discussed.METHODSBy breeding KUNMING mice, the Iung specimens of fetal (from l0 to l9 day ofgestation) and of postnatal (from neonate to adult mice) were obtained. The expressionof the polypeptides (EGFR, TGF-6l, TGF-62, TGF-63, TTF-l ) were examined byimmunohistochemistry. TIGER image analysiser was used in quantitatively studying.RESULTSl It is showed that EGFR localized in the airway surface epithelium during early3lung development and its reaction reached the peak on fetal age Day l8. In saccular andalveolar period, the positive reactions were mainly detected in alveolar cells.Bronchiolar epithelial cells expressed EGFR again after birth, and then graduallybecame weaker.2 The localization patterns in the fetal 1ung for TGF-0l, TGF-62, TGF-93 wereessentially identical. At the early period, regional expression were observed in thebronchioles. they were slighter in late gestation, but mesenchymal cells expressed athigh levels. In postnatal lung, no TGF-Pl, 62, 63 immunoreactivity was seen in thealveolar cells.3. TTF-l were expressed throughout fetal lung development, prominent in thenuclei of distal lung buds, whose staining was more intense than that of airway epithelialceIls. After birth, TTF-l was restricted to type II cells and TTF-1 became weaker inepithelial cells of trachea.4. The average optical density(AOD) of TTF-l in the distal epithelial cellsincreased gradually during the lung development. Though their volume(VOL) andvolume integrated optical density(VIOD) all decreased, the fOrmer dropped morequickly than the latter, which showed the increasing density of TTF-l and its identicalfunction with type II cells.CONCLUSIONThe positive reactions of EGFR, TGF-6l, TGF-p2, TGF-P3 and TTF-l wererespectively different during different stages, which suggests that their functions arechanging in individual developmental periods. TGF-6 inhibits lung development, but onthe contrary, EGFR and TTF-l not only stimulate the process of branchingmorphogenesis. but aIso modulate epitheIial maturation and differentiation. Normal lungdevelopment depends on the unity of two opposites.