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Hepatocyte growth factor (HGF) has multiple biological effects on stem cells, epithelial proliferation, and wound healing. In this study, we investigated a possible therapeutic benefit of intranasal HGF on elastase-induced emphysema, and assessed the role of stem/progenitor cells in this process. HGF was given twice a week for 1–4 weeks after the establishment of emphysema in mice. HGF inhalation significantly ameliorated the enlargement of airspaces and alveolar wall destruction. Also, elevated static lung compliance returned to control levels within 2 weeks of HGF treatment. The expressions of stem-cell markers, c-kit, stem-cell antigen 1 (Sca-1), and CD34 were also significantly influenced by HGF. Most of the c-kit(+) cells were bone marrow derived, while most Sca-1(+) were lung endogenous cells. CD34(+) cells were from both sources, and a portion of the endogenous CD34(+) cells was also Sca-1 …