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This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/L566    most recent 90250.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Hashimoto, S. Articles by Hashimoto, S. PubMed PubMed Citation Articles by Hashimoto, S. Articles by Hashimoto, S.

Dysregulation of lung injury and repair in moesin-deficient mice treated with intratracheal bleomycin

¹Department of Anesthesiology and Intensive Care, ²Department of Surgery, and ³Department of Cell Biology, Research Institute for Geriatrics, Kyoto Prefectural University of Medicine, Kyoto; ⁴Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai; ⁵Pulmonary Division, Department of Medicine, Keio University School of Medicine, Tokyo; and ⁶Laboratory of Biological Science, Organismal Biosystems Laboratory, Graduate School of Frontier Biosciences/Department of Pathology, Graduate School of Medicine Osaka University, Osaka, Japan

Submitted 31 March 2008 ; accepted in final form 24 July 2008

Moesin belongs to the ezrin/radixin/moesin (ERM) protein family and participates in cellular functions, such as morphogenesis and motility, by cross-linking between the actin cytoskeleton and plasma membranes. Although moesin seems necessary for tissue construction and repair, its function at the whole body level remains elusive, perhaps because of redundancy among ERM proteins. To determine the role played by moesin in the modulation of pulmonary alveolar structure associated with lung injury and repair, we examined the morphological changes in the lung and the effect of bleomycin-induced lung injury and fibrosis in moesin-deficient (Msn^–/Y) and control wild-type mice (Msn^+/Y). Immunohistochemical analysis revealed that moesin was specifically localized in the distal lung epithelium, where ezrin and radixin were faintly detectable in Msn^+/Y mice. Compared with Msn^+/Y mice, Msn^–/Y mice displayed abnormalities of alveolar architecture and, when treated with bleomycin, developed more prominent lung injury and fibrosis and lower body weight and survival rate. Furthermore, Msn^–/Y mice had abnormal cytokine and chemokine gene expression as shown by real-time PCR. This is the first report of a functional involvement of moesin in the regulation of lung inflammation and repair. Our observations show that moesin critically regulates the preservation of alveolar structure and lung homeostasis.

ezrin; radixin; lung inflammation; alveolar structure