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Increased Basigin in Bleomycin-Induced Lung Injury

Departments of Medicine and Cell Biology & Physiology, Washington University School of Medicine and Barnes-Jewish Hospital, St. Louis, Missouri; and the Department of Biochemistry, Nagoya University School of Medicine, Nagoya, Japan

Address correspondence to: Tomoko Betsuyaku, First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan. E-mail: bytomoko{at}med.hokudai.ac.jp

Basigin is expressed in many tissues during development, including lung. It is also found on tumor cells and in wounds where it is thought to stimulate adjacent fibroblasts to produce matrix metalloproteinases. To investigate whether basigin might be expressed in fibro-inflammatory lung processes, we generated bleomycin-induced lung injury in mice. At 14 d after intratracheal bleomycin, we found basigin prominently in areas of fibrosis, alveolar macrophages, and bronchiolar epithelium, whereas it was only weakly present in bronchiolar epithelium in untreated mice. Western blots of radioimmunoprecipitation assay RIPA-insoluble fractions of bleomycin-treated lungs showed increased basigin compared with RIPA-insoluble fractions of lung from untreated mice. By quantitative reverse transcriptase-polymerase chain reaction, lung basigin mRNA was significantly increased 14 d after bleomycin, and by in situ hybridization, basigin mRNA was prominent in bronchiolar epithelium. Western blots of bronchoalveolar lavage fluid (BALF) showed various forms of basigin after bleomycin that were not present in BALF from untreated lung. These results demonstrate that bleomycin-induced lung injury is associated with increased basigin expression in bronchiolar epithelium, deposition of basigin in fibrotic sites, and increased basigin in BALF. Accordingly, basigin may play a role in diffuse alveolar injury.

Abbreviations: bronchoalveolar lavage fluid, BALF • extracellular, EC • glyceraldehyde-3-phosphatase dehydrogenase, GAPDH • glutathione-S-transferase, GST • matrix metalloproteinase, MMP • phosphate-buffered saline, PBS • polymerase chain reaction, PCR • sodium dodecyl sulfate, SDS

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