Periostin Deficiency Causes Severe and Lethal Lung Injury in Mice With Bleomycin Administration.
Pulmonary capillary leakage followed by influx of blood fluid into the air space of lung alveoli is a crucial step in the progression of acute lung injury (ALI). This influx is due to increased permeability of the alveolar-capillary barrier. The extracellular matrix (ECM) between the capillary and the epithelium would be expected to be involved in prevention of the influx; however, the role of the ECM remains to be addressed. Here, we show that the ECM architecture organized by periostin, a matricellular protein, plays a pivotal role in the survival of bleomycin-exposed mice. Periostin was localized in the alveolar walls. Although periostin-null mice displayed no significant difference in lung histology and air-blood permeability, they exhibited early lethality in a model of bleomycin-induced lung injury, compared with their wild-type counterparts. This early lethality may have been due to increased pulmonary leakage of blood fluid into the air space in the bleomycin-exposed periostin-null mice. These results suggest that periostin in the ECM architecture prevents pulmonary leakage of blood fluid, thus increasing the survival rate in mice with ALI. Thus, this study provides an evidence for the protective role of the ECM architecture in the lung alveoli.
Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan (HK, TN, IK, AK)
Hirofumi
H
Kondoh
Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan (HK, TN, IK, AK)
Takashi
T
Nishiyama
Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan (YK, MF)
Yoshinao
Y
Kikuchi
Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan (YK, MF)
Masashi
M
Fukayama
Department of Orthopaedic Surgery, Jikei University School of Medicine, Tokyo, Japan (MS)
Mitsuru
M
Saito
Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan (HK, TN, IK, AK)|Pathophysiological and Health Science Team, Imaging Application Group, Division of Bio-Function Dynamics Imaging, RIKEN Center for Life Science Technologies, Kobe, Japan (IK)
Isao
I
Kii
Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan (HK, TN, IK, AK)
Akira
A
Kudo
D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D017398:Alternative Splicing; D000818:Animals; D001761:Bleomycin; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000502:physiology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011650:Pulmonary Alveoli / Q000473:pathology / Q000648:ultrastructure
D015815:Cell Adhesion Molecules; C082838:Postn protein, mouse; D001761:Bleomycin; D003094:Collagen
acute lung injury; alveolus; bleomycin; collagen; extracellular matrix; fibronectin; matricellular; periostin; pulmonary leakage; stroma