Hepatocyte growth factor induces angiogenesis in injured lungs through mobilizing endothelial progenitor cells.
Circulating endothelial progenitor cells (EPCs) play a pivotal role in angiogenesis. Hepatocyte growth factor (HGF) is known to induce proliferation and motility in endothelial cells, and to play a role in mitogenic and morphogenic actions. However, the role of HGF in EPC mobilization has not been clearly described yet. We investigated the effect of HGF on mobilizing EPCs and on angiogenesis in elastase-induced lung injury. HGF significantly increased the triple-positive (Sca-1(+), Flk-1(+), and c-kit(+)) fraction in peripheral mononuclear cells in mice. The bone marrow-derived cells were recruited into the injured lungs, where they differentiated to capillary endothelial cells. HGF induced proliferation of both bone marrow-derived and resident endothelial cells in the alveolar wall. In conclusion, the present study suggests that HGF induces EPC mobilization from the bone marrow and enhances the proliferation of endothelial cells in vivo. These complex effects induced by HGF orchestrate pulmonary regeneration in emphysematous lung parenchyma.
Ishizawa
Kota
K
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, Miyagi 980-8574, Japan.
Kubo
Hiroshi
H
Yamada
Mitsuhiro
M
Kobayashi
Seiichi
S
Suzuki
Takashi
T
Mizuno
Shinya
S
Nakamura
Toshikazu
T
Sasaki
Hidetada
H
D000818:Animals; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000502:physiology; D002454:Cell Differentiation; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D049408:Luminescent Agents / Q000378:metabolism; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic; D010196:Pancreatic Elastase / Q000633:toxicity; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
D015415:Biomarkers; D049408:Luminescent Agents; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor; D010196:Pancreatic Elastase