Two Different Patterns of Airway Branching Regulated by Different Components of the Extracellular Matrix in Vitro

Abstract

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.

Normal Patterns of Angiogenesis and Extracellular Matrix Deposition in Chick Chorioallantoic Membranes Are Disrupted by Mainstream and Sidestream Cigarette Smoke

“…The extracellular matrix plays important roles in regulating many developmental processes, including angiogenesis and branching morphogenesis (Hisaoka et al, 1993;Matsui et al, 1996). In the CAM, the extracellular matrix undergoes compositional changes (Ausprunk, 1986;Ausprunk et al, 1991; that are known to be important in influencing blood vessel development (Ingber, 1991(Ingber, , 1992, although the exact effects of individual matrix components are not yet fully understood.…”

Effect of triamcinolone acetonide on the development of the pulmonary airways in the fetal rat

“…21 Our own data indicate that monopodial branching and dichotomous branching are affected differently by cis-hydroxyproline and Bxyloside, antagonists to collagen and proteoglycan synthesis, respectively (cis-hydroxyproline affects dichotomous branching and B-xyloside monopodial branching). 22,23 It thus seems that they are fundamentally different processes and that TAC affects primarily monopodial branching. Second, it may or may not seem intuitively correct that lung growth, morphogenesis, tissue maturation (e.g., alveolar formation), and differentiation would be affected similarly when lung development is abnormal.…”

Lung stem cells

“…Foetal (E15) rat organ cultures were studied for the effects of proteoglycan and collagen synthesis on branching morphogenesis (Matsui et al 1996). Inhibitors of proteoglycan synthesis resulted in a static lung size, with larger air spaces and less mesenchymal tissue and fewer proximal branching events.…”