Amphiregulin, an
EGF receptor (EGFR)
ligand, is essential for epithelial development in various organs. A recent report suggested that
amphiregulin acts as a protective factor in a liver injury model. Little is known about the roles of
amphiregulin in
lung injury and
pulmonary fibrosis. The purpose of the present study was to investigate the role of
amphiregulin in an experimental model of
bleomycin-induced pneumopathy in mice. C57BL/6 mice were administered a
bleomycin hydrochloride
solution intratracheally. Recombinant human
amphiregulin was injected intraperitoneally at 6, 8, 10, and 12 days after the
bleomycin instillation. The grades of
inflammation and
fibrosis were assessed histologically and biochemically, and the numbers of apoptotic cells were counted after TdT-mediated dUTP nick end labeling (TUNEL) staining in the lung tissues. We also examined downstream survival signals of EGFR, namely phosphorylated Akt and phosphorylated Erk, in lung tissues by Western blotting analysis and immunohistochemistry. Expression of intrinsic
amphiregulin was increased in murine lung tissues after
bleomycin instillation. Administration of recombinant
amphiregulin improved the survival rate and suppressed the degrees of
inflammation and
fibrosis and the number of TUNEL-positive cells in lung tissues.
Amphiregulin treatment enhanced the activation of Akt and Erk in lung epithelial cells.
Amphiregulin may play a protective role
in bleomycin-induced pneumopathy in mice, probably through the activation of survival signals. Administration of
amphiregulin may be a novel therapeutic strategy against
lung injury and
fibrosis.