Epimorphin expression in interstitial pneumonia.
Epimorphin modulates epithelial morphogenesis in embryonic mouse organs. We previously suggested that epimorphin contributes to repair of bleomycin-induced pulmonary fibrosis in mice via epithelium-mesenchyme interactions. To clarify the role of epimorphin in human lungs, we evaluated epimorphin expression and localization in normal lungs, lungs with nonspecific interstitial pneumonia (NSIP), and lungs with usual interstitial pneumonia (UIP); we also studied the effect of recombinant epimorphin on cultured human alveolar epithelial cells in vitro. Northern and Western blotting analyses revealed that epimorphin expression in NSIP samples were significantly higher than those in control lungs and lungs with UIP. Immunohistochemistry showed strong epimorphin expression in mesenchymal cells of early fibrotic lesions and localization of epimorphin protein on mesenchymal cells and extracellular matrix of early fibrotic lesions in the nonspecific interstitial pneumonia group. Double-labeled fluorescent images revealed expression of matrix metalloproteinase 2 in re-epithelialized cells overlying epimorphin-positive early fibrotic lesions. Immunohistochemistry and metalloproteinase activity assay demonstrated augmented expression of metalloproteinase induced by recombinant epimorphin in human alveolar epithelial cells. These findings suggest that epimorphin contributes to repair of pulmonary fibrosis in nonspecific interstitial pneumonia, perhaps partly by inducing expression of matrix metalloproteinase 2, which is an important proteolytic factor in lung remodeling.
Terasaki
Yasuhiro
Y
Department of Cell Pathology, Postgraduate School of Medicine, Kumamoto University, Kumamoto, Japan. terayasu@kaiju.medic.kumamoto-u.ac.jp
Fukuda
Yuh
Y
Suga
Moritaka
M
Ikeguchi
Naoki
N
Takeya
Motohiro
M
D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000378:metabolism* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D050827:Syntaxin 1; D014018:Tissue Distribution
D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; C074558:STX2 protein, human; D050827:Syntaxin 1; D020778:Matrix Metalloproteinase 2