Oncostatin M modulates fibroblast function via signal transducers and activators of transcription proteins-3

Kumi Yoneda Nagahama, Shinsaku Togo, Olaf Holz, Helgo Magnussen, Xiang-de Liu, Kuniaki Seyama, Kazuhisa Takahashi, Stephen I. Rennard

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

OncostatinM(OSM), an inflammatory cytokine of the interleukin-6 (IL-6) superfamily, plays a key role in various biological processes such as modulation of extracellular matrix (ECM), cell proliferation, cell survival, and induction of inflammation. It has been reported that OSM was increased in asthma and pulmonary fibrosis, and thus OSM may play a role in airway remodeling and the development of lung parenchymal fibrosis. Recruitment of lung fibroblasts to the sites of airway injury and subsequent differentiation into myofibroblasts is believed to contribute to excess ECM deposition. In the current study, we assessed the ability ofOSMto modulate fibroblast collagen gel contraction, migration toward fibronectin, and expression of a-smooth muscle actin (a-SMA). We demonstrated that OSMaugments gel contraction, chemotaxis, and a-SMA expression. OSM-augmented fibroblast chemotaxis was mediated by the signal transducer and activator of transcription (STAT3) and p38 mitogenactivated protein kinase, while augmentation on gel contraction and a-SMA expression was mediated by STAT3. Neither transforming growth factor-b1 nor PGE2 was involved in mediating OSM effect on the cells. The Th2 cytokines IL-4 and IL-13, which also are believed to play an important role in promoting lung fibrosis and airway remodeling, act through STAT3, and we demonstrated the potential for additive effects of OSM with IL-4 and IL-13. The present study supports the concept that OSM may contribute to tissue remodeling, which may be additive with IL-4 or IL-13. Blockade of OSM or OSM-mediated STAT3 signaling could be a therapeutic target to regulate lung fibrotic mechanisms.

Original languageEnglish (US)
Pages (from-to)582-591
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume49
Issue number4
DOIs
Publication statusPublished - Oct 1 2013

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Keywords

  • Asthma
  • Chemotaxis
  • Contractility
  • Fibrosis

ASJC Scopus subject areas

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

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