Browsing by Author "Uchida, Masaru"

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    Periostin, a matricellular protein, plays a role in the induction of chemokines in pulmonary fibrosis
    (American Thoracic Society, 2012-05) Uchida, Masaru; Shiraishi, Hiroshi; Ohta, Shoichiro; Arima, Kazuhiko; Taniguchi, Kazuto; Suzuki, Shoichi; Okamoto, Masaki; Ahlfeld, Shawn K.; Ohshima, Koichi; Kato, Seiya; Toda, Shuji; Sagara, Hironori; Aizawa, Hisamichi; Hoshino, Tomoaki; Conway, Simon J.; Hayashi, Shinichiro; Izuhara, Kenji; Department of Pediatrics, IU School of Medicine
    Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and usually fatal form of interstitial lung disease (ILD). The precise molecular mechanisms of IPF remain poorly understood. However, analyses of mice receiving bleomycin (BLM) as a model of IPF established the importance of preceding inflammation for the formation of fibrosis. Periostin is a recently characterized matricellular protein involved in modulating cell functions. We recently found that periostin is highly expressed in the lung tissue of patients with IPF, suggesting that it may play a role in the process of pulmonary fibrosis. To explore this possibility, we administered BLM to periostin-deficient mice, and they subsequently showed a reduction of pulmonary fibrosis. We next determined whether this result was caused by a decrease in the preceding recruitment of neutrophils and macrophages in the lungs because of the lower production of chemokines and proinflammatory cytokines. We performed an in vitro analysis of chemokine production in lung fibroblasts, which indicated that periostin-deficient fibroblasts produced few or no chemokines in response to TNF-α compared with control samples, at least partly explaining the lack of inflammatory response and, therefore, fibrosis after BLM administration to periostin-deficient mice. In addition, we confirmed that periostin is highly expressed in the lung tissue of chemotherapeutic-agent-induced ILD as well as of patients with IPF. Taking these results together, we conclude that periostin plays a unique role as an inducer of chemokines to recruit neutrophils and macrophages important in the process of pulmonary fibrosis in BLM-administered model mice. Our results suggest a therapeutic potential for periostin in IPF and drug-induced ILD.