Am. J. Respir. Cell Mol. Biol.,
Volume 23, Number 2, August, 2000 168-174
Increased Expression of Epimorphin in Bleomycin-Induced
Pulmonary Fibrosis in Mice
Yasuhiro
Terasaki,
Yuh
Fukuda,
Masamichi
Ishizaki,
and
Nobuaki
Yamanaka
Department of Pathology, Nippon Medical School, Tokyo; Department of First Internal Medicine, Kumamoto University,
School of Medicine, Kumamoto, Japan
Epimorphin was originally identified as a mesenchymal, cell
surface-associated protein that modulates epithelial morphogenesis in embryonic organs, whereas pulmonary fibrosis is a
process of wound healing, which in part mimics the process of
fetal lung development. We investigated the temporal and spatial changes in the distribution of epimorphin protein and expression of its messenger RNA (mRNA) in bleomycin-induced
pulmonary fibrosis in mice. Immunohistochemical analysis
showed that low levels of epimorphin were present in the bronchiolar, alveolar, and vascular walls of normal adult lungs.
However, from Day 7 until Day 28 after bleomycin treatment,
increasing levels of epimorphin immunoreactivity were detected in the mesenchymal cells and in the extracellular matrix within intra-alveolar fibrotic lesions. Moreover, Northern blots showed corresponding increases in epimorphin mRNA
expression. Re-epithelialization of epimorphin-rich intra-alveolar fibrosis was complete by Day 28 after bleomycin, and by
Day 56, epimorphin immunoreactivity had declined. In situ hybridization and confocal microscopic studies confirmed expression of epimorphin mRNA by mesenchymal cells situated
within early fibrotic lesions, whereas immunoelectron microscopy localized the epimorphin to the endoplasmic reticulum
of the mesenchymal cells and to the basement membrane and
collagen fibrils in the area. These results suggest that epimorphin may contribute to the remodeling of pulmonary fibrosis
via epithelial-mesenchymal interactions.
