We previously reported (Gray, T. E., K. Guzman, C. W. Davis, L. H. Abdullah, and P. Nettesheim. 1996. Mucociliary differentiation of serially passaged normal @entity1 tracheobronchial epithelial cells. Am. J. Respir. Cell Mol. Biol. 14:104-112) that @entity1968 (RA)-deprived cultures of normal @entity1 tracheobronchial epithelial (NHTBE) cells became squamous, failed to produce @entity3558 , and instead secreted or released large amounts of @entity16977 (LZ). The purpose of the studies reported here was to elucidate the relationship between @entity7245 -induced squamous differentiation and increased LZ, and to determine what mechanisms were involved. We found that intracellular LZ began to accumulate in @entity7245 NHTBE cultures early during squamous differentiation. Between Days 10 and 18 of culture, cellular LZ levels were more than 10 times higher in @entity7245 than in RA-sufficient cultures. On Day 12, large numbers of cells began to exfoliate in @entity7245 cultures and extracellular LZ appeared at the apical surface, presumably released from the exfoliated cells. Metabolic labeling studies showed that the rate of LZ synthesis was not increased in @entity7245 cultures over that in RA-sufficient cultures; however, intracellular LZ half-life was much longer in @entity7245 cultures. We concluded that the increased accumulation of both intra- and extracellular LZ in @entity7245 cultures was due to increased LZ stability and was not the result of increased LZ synthesis. When @entity7245 cultures were treated on Day 7 with 10(-6) M RA, intracellular LZ levels did not substantially decrease until 3 d later, coinciding with a marked increase in @entity3558 secretion. LZ messenger RNA levels were unchanged at 24 h, but were modestly increased (rather than decreased) at all subsequent time points. We concluded that RA does not directly regulate LZ, and that the excessive accumulation of LZ in RA-deprived NHTBE cells is a consequence of @entity904 deficiency-induced abnormal differentiation.

@entity16977 expression during metaplastic squamous differentiation of @entity1968 -deficient XXXX tracheobronchial epithelial cells.

@entity1 :: ('9606', 'Species') :: ['human'] @entity16977 :: ('4069', 'Gene') :: ['lysozyme'] @entity7245 :: ('MESH:D000592', 'Disease') :: ['RA-deficient', 'RA deficiency'] @entity904 :: ('MESH:D014801', 'Chemical') :: ['vitamin A'] @entity3558 :: ('100508689', 'Gene') :: ['mucin'] @entity1968 :: ('MESH:D014212', 'Chemical') :: ['retinoic acid']
@entity1 :: (9606,Species) :: ['human']
