Modification of mucin gene expression in the airways of rats exposed to sulfur dioxide.
The molecular mechanisms mediating mucous cell metaplasia and hypersecretion in the respiratory tract are unknown. Previous work suggests that mucous metaplasia requires the induction of mucin gene expression. We are investigating this possibility by monitoring steady state levels of mucin mRNA in a model of mucous cell metaplasia induced by SO2 exposure. Male Sprague Dawley rats were exposed to 400 ppm SO2 gas in air for 3 h per day, 5 days per week for 0,1,2, or 3 weeks. Sham controls were exposed to air under similar conditions. After 3 weeks, morphological changes were apparent in the epithelium of SO2 exposed rats at all levels from the trachea to the distal airways. The epithelial thickness increased, as well as the number and size of glands in the trachea. Epithelial mucous (goblet) cells increased from 0 to 4.5 per mm in the trachea, 0.2 to 6.2 per mm in the main stem bronchi, and 0.2 to 22.7 per mm in the distal airways (mean values obtained for 3-6 tissue blocks per airway level per condition). In parallel experiments, we used SMUC41, a 950 bp human intestinal cDNA to isolate a human airway cDNA, HAM-1 from a cDNA library constructed in bacteriophage from human bronchial poly A+RNA. HAM-1 is a 90 bp cDNA encoding a threonine- and proline-rich peptide with 96% homology to the human intestinal cDNA SMUC-41. Next we probed total and poly A+ airway RNA from rats in each exposure condition with SMUC-41 or HAM-1. Blots were then stripped and reprobed with cDNA encoding beta actin. Densitometry values normalized for the amount of RNA loaded per lane (as determined by actin hybridization intensity) showed that mucin mRNA increased 8-9 fold as a function of SO2 exposure. This is consistent with the possibility that mucin gene transcription is induced by SO2 exposure, and may represent a primary event in the development of mucous metaplasia and hypersecretion.
Basbaum
C
C
Department of Anatomy, University of California, San Francisco.
Gallup
M
M
Gum
J
J
Kim
Y
Y
Jany
B
B
D000818:Animals; D004195:Disease Models, Animal; D004848:Epithelium / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D008679:Metaplasia; D009077:Mucins / Q000235:genetics*; D009092:Mucous Membrane / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012137:Respiratory System / Q000473:pathology*; D013458:Sulfur Dioxide / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D009077:Mucins; D012333:RNA, Messenger; D013458:Sulfur Dioxide