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Originally published as JHC exPRESS on May 3, 2007.
doi:10.1369/jhc.7A7203.2007
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Journal of Histochemistry and Cytochemistry
Volume 55 (9): 899-909, 2007
Copyright ©The Histochemical Society, Inc.

Loss of Caveolin-1 in Bronchiolization in Lung Fibrosis

Nao Odajima, Tomoko Betsuyaku, Yasuyuki Nasuhara and Masaharu Nishimura

First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan

Correspondence to: Tomoko Betsuyaku, MD, PhD, First Department of Medicine, Hokkaido University School of Medicine, N-15, W-7, Kita-ku, Sapporo 060-8638, Japan. E-mail: bytomoko{at}med.hokudai.ac.jp

Bronchiolization is a key process in fibrosing lung in which the proliferative status of bronchiolar epithelium changes, leading to abnormal epithelial morphology. Within the context that caveolin-1 acts to suppress epithelial proliferation, we postulated that stimulating epithelial injury would lead to caveolin-1 downregulation and encourage proliferation. The present study evaluates the expression of caveolin-1, especially in bronchiolization, in C57BL/6J mice with bleomycin-induced lung fibrosis and in various types of re-epithelialization in human interstitial pneumonias (IPs). Immunohistochemically, levels of caveolin-1 decreased in the bronchiolar epithelium of mice treated with bleomycin. Levels of caveolin-1 mRNA in the whole lung were decreased at 7 and 14 days. Caveolin-1 mRNA was also decreased in laser-capture microdissection- retrieved bronchiolar epithelial cells at 7 days. Among patients with 12 IPs, including four usual IPs (UIPs) and eight nonspecific IPs (NSIPs), whole lung caveolin-1 was significantly decreased compared with 12 controls at both mRNA and protein levels. By scoring immunointensity, caveolin-1 was significantly reduced in bronchiolization and squamous metaplasia as well as in bronchiolar epithelium in 23 IPs (12 UIPs and 11 NSIPs) compared with bronchiolar epithelium from seven controls. These data suggested that loss of caveolin-1 is associated with abnormal re-epithelialization in lung fibrosis. (J Histochem Cytochem 55:899–909, 2007)

Key Words: caveolin-1 • bleomycin • lung fibrosis • bronchiolization • laser-capture microdissection


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