マウス胎児肺および肺気腫モデルにおけるWNTとそのインヒビター(FRP1)の発現

概要

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The airway patterning is orchestrated under the control of morphogens in a spatiotemporal manner. Fgf, Bmp, Wnt and Hedgehog are critical determinants for the developmental morphogenesis through their reiterative and reciprocal interaction. To understand the role in organogenesis, it is an important issue to localize the expression domain in the active signaling center. However, Wnt expression in the airway development is not clearly demonstrated yet. In the present study, we examined Wnt5a, Wut10b and secreted frizzled-related protein 1 (Frp1) expression in the developing mouse lungs. These molecules were present in the embryo lungs but not in the postnatal lungs at RNA and protein levels. Immunohistochemical staining and in situ hybridization showed that Wnt5a and Frp1 were localized to the distal airway epithelium and surrounding mesenchyme, and Wnt10b in the distal epithelial cells. The immunoreaction was detected until 16.5 days post-coitum. These data suggest an involvement of the Wnt signaling and an interaction with other morphogen signaling in the lung development. Frp1 expression also suggests a role of the Wnt inhibitory machinery to demarcate the Wnt activity in the active signaling center. Re-activation of Frp1 gene expression in mouse models of pulmonary emphysema might implicate a role of inadequate activation of developmental gene in the pathophysiology of pulmonary emphysema.
日本結合組織学会の論文