Two different patterns of airway branching regulated by different components of the extracellular matrix in vitro.
This study examined the effects of beta-D-xyloside (an inhibitor of proteoglycan synthesis) and cis-4-hydroxyl-L-proline (an inhibitor of collagen synthesis) on branching morphogenesis in cultures of fetal rat lung. Lungs from day 15 gestation were incubated for 4 days in (1) the control medium (Dulbecco's Modified Eagle Medium + 10% Fetal Bovine Serum) alone (control), (2) control medium plus 2 mM beta-D-xyloside (beta-XYL), (3) control medium plus 2 mM alpha-D-xyloside (alpha-XYL), (4) control medium plus 50 micrograms/mL cis-4-hydroxy-L-proline (cis-HYP). The number of peripheral buds of left lungs was counted daily. Histological examination was performed on lungs on days 2 and 4. beta-XYL inhibited proximal monopodial branching on day 2 without affecting lung size, but produced numerous peripheral buds on day 4 which were of abnormal appearance, suggesting that lung airway branching and growth may be regulated by different mechanisms. Histology and morphometry showed significantly enlarged airspaces and diminished mesenchyme. cis-HYP did not affect proximal branching on 2 days in culture, but inhibited further dichotomous branching and lung growth after 2 days. On day 4, diminished branching and lung growth was accompanied by a proportional decrease in mesenchyme. The difference between effects of beta-XYL and cis-HYP on the branching pattern suggests that proteoglycans and collagen are involved in different patterns of branching morphogenesis.
Matsui
R
R
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
Thurlbeck
W M
WM
Shehata
E I
EI
Sekhon
H S
HS
D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D046508:Culture Techniques; D005109:Extracellular Matrix / Q000502:physiology*; D005260:Female; D006027:Glycosides / Q000494:pharmacology; D006909:Hydroxyproline / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D006027:Glycosides; C010807:xylosides; D006909:Hydroxyproline