Periostin, a matricellular protein, plays a role in the induction of chemokines in pulmonary fibrosis

Masaru Uchida, Hiroshi Shiraishi, Shoichiro Ohta, Kazuhiko Arima, Kazuto Taniguchi, Shoichi Suzuki, Masaki Okamoto, Shawn K. Ahlfeld, Koichi Ohshima, Seiya Kato, Shuji Toda, Hironori Sagara, Hisamichi Aizawa, Tomoaki Hoshino, Simon J. Conway, Shinichiro Hayashi, Kenji Izuhara

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)677-686
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume46
Issue number5
DOIs
StatePublished - May 2012

Keywords

  • Bleomycin
  • Chemokine
  • Extracellular matrix protein
  • Idiopathic pulmonary fibrosis
  • Matricellular protein

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

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