Differential expression of the glycosylated forms of MUC1 during lung development.
Human MUC1 mucin is a high-molecular weight transmembrane glycoprotein expressed on the apical surface of the simple epithelia of many different tissues. Previous investigations suggest the involvement of MUC1 in epithelial cytodifferentiation and glandular morphogenesis. However, the role of MUC1 in the development of the fetal respiratory tracts has so far been poorly investigated. To obtain more information on the roles of MUC1 during fetal lung development, we examined the expression and distribution of MUC1 by immunohistochemical staining of postmortem lung specimens from fetuses and neonates of various gestational ages. Three monoclonal antibodies, HMFG1, HMFG2, and anti-KL-6, which bind different glycosylation variants, were used. Each monoclonal antibody has been shown to recognize heavily-glycosylated MUC1, sparsely-glycosylated MUC1, and sialylated carbohydrate side chains of MUC1, respectively. At 13 weeks of gestation, the terminal respiratory tracts were diffusely stained with HFMG1 and anti-KL-6. Sparsely-glycosylated MUC1, as recognized by HMFG2, was detected only in the distal portions of the terminal bronchioles that divided into respiratory bronchioles. As such development continued, MUC1, recognized by HMFG1 and anti-KL-6, was detected throughout the bronchioles and terminal sacs, although HMFG1 immunoreactivity decreased in intensity towards the terminal sacs. Sparsely-glycosylated MUC1, as recognized by HMFG2, was mainly observed in the terminal portions. In the adult lungs, both the alveolar spaces and the respiratory bronchioles stained with HFMG1 and anti-KL-6. However, the distribution of sparsely-glycosylated MUC1 was limited in the alveolar epithelial cells. Our investigation demonstrated that variants of MUC1 were expressed in the fetal respiratory tracts as early as 13 weeks of gestation, and its expression persisted even after lung maturation. The precise roles of MUC1 were not determined in the present study; however, different glycosylation variants of MUC1 may be associated with the development of different regions of the terminal respiratory tract.
Department of Molecular and Internal Medicine, Graduate School of Biochemical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
J
J
Sakurai
N
N
Hattori
M
M
Nakajima
T
T
Moriya
T
T
Suzuki
A
A
Yokoyama
N
N
Kohno
D000328:Adult; D005333:Fetus / Q000196:embryology / Q000378:metabolism; D005865:Gestational Age; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D008168:Lung / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism*; D018396:Mucin-1 / Q000737:chemistry / Q000378:metabolism*
C060192:MUC1 protein, human; D018396:Mucin-1