TY - JOUR
T1 - Intranasal HGF administration ameliorates the physiologic and morphologic changes in lung emphysema
AU - Hegab, Ahmed E.
AU - Kubo, Hiroshi
AU - Yamaya, Mutsuo
AU - Asada, Masanori
AU - He, Mei
AU - Fujino, Naoya
AU - Mizuno, Shinya
AU - Nakamura, Toshikazu
N1 - Funding Information:
We thank Masaru Okabe (Genome Information Research Center, Osaka University, Japan) for providing GFP-transgenic mice (C57BL/6 TgN(act-GFP) OsbC14-Y01-FM131). This work was supported by grant No. 19390222 from the Japan Society for the Promotion of Science to H. Kubo. A.E.H. is a Research Fellow of the Japan Society for the Promotion of Science. This work was done in Sendai city, Miyagi Prefecture, Japan. The authors declared no conflict of interest.
PY - 2008/8
Y1 - 2008/8
N2 - 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(+). Further, HGF increased the expression levels of proliferating cell nuclear antigen (PCNA) and cytokeratin-19. Also, their immunohistochemical staining patterns were colocalized, indicative of epithelial multiplication. The results of the study show that intranasal treatment with HGF reverses both the physiological and morphometric changes of lung emphysema, possibly through stem-cell mobilization and alveolar regeneration, providing a nonsurgical treatment and suggesting the possibility of achieving a similar effect in humans.
AB - 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(+). Further, HGF increased the expression levels of proliferating cell nuclear antigen (PCNA) and cytokeratin-19. Also, their immunohistochemical staining patterns were colocalized, indicative of epithelial multiplication. The results of the study show that intranasal treatment with HGF reverses both the physiological and morphometric changes of lung emphysema, possibly through stem-cell mobilization and alveolar regeneration, providing a nonsurgical treatment and suggesting the possibility of achieving a similar effect in humans.
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U2 - 10.1038/mt.2008.137
DO - 10.1038/mt.2008.137
M3 - Article
C2 - 18560414
AN - SCOPUS:48349135195
SN - 1525-0016
VL - 16
SP - 1417
EP - 1426
JO - Molecular Therapy
JF - Molecular Therapy
IS - 8
ER -