Rad9 is upregulated and plays protective roles in an acute lung injury model.
The Rad9-Hus1-Rad1 protein complex is believed to respond to DNA damage and play important roles in the cell cycle. We studied the role of Rad9 protein in alveolar epithelial cells in the pathogenesis of acute lung injury. In a mouse model of lung injury induced by bleomycin or lipopolysaccharide, Rad9 expression is increased in type II alveolar epithelial cells from the early stage of lung injury. A549 cells and mouse primary alveolar epithelial cells also upregulated Rad9 expression after exposure to bleomycin. Gene silencing of Rad9 using siRNA decreased the G2/M arrest in A549 cells induced by bleomycin and also decreased the survival of A549 cells following exposure to bleomycin and hydrogen peroxide. In conclusion, Rad9 is a signal in the earlier stage of epithelial cell cycle regulation and plays protective roles in alveolar epithelial cells in the pathogenesis of acute lung injury.
Yamamoto
Masatsugu
M
Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunokicho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
Nishiuma
Teruaki
T
Kobayashi
Kazuyuki
K
Maniwa
Yoshimasa
Y
Sakashita
Akihiro
A
Funada
Yasuhiro
Y
Kotani
Yoshikazu
Y
Nishimura
Yoshihiro
Y
D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D020868:Gene Silencing; D006861:Hydrogen Peroxide / Q000633:toxicity; D051379:Mice; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
D018797:Cell Cycle Proteins; D034741:RNA, Small Interfering; D001761:Bleomycin; C069930:rad9 protein; D006861:Hydrogen Peroxide