TY - JOUR
T1 - Cloning of rat fibrillin-2 cDNA and its role in branching morphogenesis of embryonic lung
AU - Yang, Qiwei
AU - Ota, Kosuke
AU - Tian, Yufeng
AU - Kumar, Anil
AU - Wada, Jun
AU - Kashihara, Naoki
AU - Wallner, Elisabeth
AU - Kanwar, Yashpal S.
N1 - Funding Information:
This work was supported by NIH Grant DK28492.
PY - 1999/8/1
Y1 - 1999/8/1
N2 - Fibrillin-2 is an extracellular matrix protein. It is associated with elastic fibers in several tissues and is believed to serve as a ligand for αvβ3 integrin, the latter being a known morphogen. In this study, the role of fibrillin-2 in lung development was investigated. Also, rat fibrillin-2 cDNA was isolated and sequenced and its spatiotemporal expression determined. It had ~88% homology with human fibrillin-2 and had Ca2+ binding epidermal growth factor-like domains, transforming growth factor-β binding protein motifs, and two RGD binding sites. Northern blot analysis revealed an ~10-kb transcript, and fibrillin-2 expression was developmentally regulated, and it paralleled that of tropoelastin. At day 13 of gestation, fibrillin-2 was expressed in the mesenchyme and at the epithelial:mesenchymal interface. From day 13 to 19 of gestation, its expression intensified and was confined around the tracheobronchial airways, while it lessened during the postnatal period. Immunoprecipitation revealed an ~350-kDa band by SDS-PAGE. Treatment with fibrillin-2 antisense oligodeoxynucleotide induced dysmorphogenesis of the lung explants. They were smaller and had rudimentary lung bud branches, collapsed conducting airways, and loose expanded mesenchyme. Concomitantly, fibrillin-2 mRNA, antibody reactivity in the explants, and fibrillin-2- specific radioincorporation were reduced. Anti-αv and -laminin antibody reactivity and their respective incorporated specific radioactivities were unaltered. These data indicate that fibrillin-2 modulates organogenesis of the lung in the context of epithelial:mesenchymal interactions. Conceivably, the collapse of the conducting airways may also be related to the perturbed biology of the fibrillin-2 interacting protein, i.e., elastin, the latter being critical for the normal biophysiology of the lungs.
AB - Fibrillin-2 is an extracellular matrix protein. It is associated with elastic fibers in several tissues and is believed to serve as a ligand for αvβ3 integrin, the latter being a known morphogen. In this study, the role of fibrillin-2 in lung development was investigated. Also, rat fibrillin-2 cDNA was isolated and sequenced and its spatiotemporal expression determined. It had ~88% homology with human fibrillin-2 and had Ca2+ binding epidermal growth factor-like domains, transforming growth factor-β binding protein motifs, and two RGD binding sites. Northern blot analysis revealed an ~10-kb transcript, and fibrillin-2 expression was developmentally regulated, and it paralleled that of tropoelastin. At day 13 of gestation, fibrillin-2 was expressed in the mesenchyme and at the epithelial:mesenchymal interface. From day 13 to 19 of gestation, its expression intensified and was confined around the tracheobronchial airways, while it lessened during the postnatal period. Immunoprecipitation revealed an ~350-kDa band by SDS-PAGE. Treatment with fibrillin-2 antisense oligodeoxynucleotide induced dysmorphogenesis of the lung explants. They were smaller and had rudimentary lung bud branches, collapsed conducting airways, and loose expanded mesenchyme. Concomitantly, fibrillin-2 mRNA, antibody reactivity in the explants, and fibrillin-2- specific radioincorporation were reduced. Anti-αv and -laminin antibody reactivity and their respective incorporated specific radioactivities were unaltered. These data indicate that fibrillin-2 modulates organogenesis of the lung in the context of epithelial:mesenchymal interactions. Conceivably, the collapse of the conducting airways may also be related to the perturbed biology of the fibrillin-2 interacting protein, i.e., elastin, the latter being critical for the normal biophysiology of the lungs.
KW - CDNA cloning
KW - Extracellular matrix
KW - Fibrillin
KW - Lung development
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U2 - 10.1006/dbio.1999.9331
DO - 10.1006/dbio.1999.9331
M3 - Article
C2 - 10419698
AN - SCOPUS:0033178557
SN - 0012-1606
VL - 212
SP - 229
EP - 242
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -