CCN6 as a profibrotic mediator that stimulates the proliferation of lung fibroblasts via the integrin β1/focal adhesion kinase pathway

• Published in: The Journal of Medical Investigation Vol. 58; no. 3,4; pp. 188 - 196
• Main Authors: Batmunkh, Rentsenkhand, Nishioka, Yasuhiko, Aono, Yoshinori, Azuma, Momoyo, Kinoshita, Katsuhiro, Kishi, Jun, Makino, Hideki, Kishi, Masami, Takezaki, Akio, Sone, Saburo
• Format: Journal Article
• Language: English
• Published: The University of Tokushima Faculty of Medicine 2011
• Subjects: CCN; fibroblasts; focal adhesion kinas; integrin; proliferation
• ISSN: 1343-1420; 1349-6867
• DOI: 10.2152/jmi.58.188

Idiopathic pulmonary fibrosis is a progressive and lethal disease of the lung that is characterized by the proliferation of fibroblasts and increased deposition of the extracellular matrix. The CCN6/WISP-3 is a member of the CCN family of matricellular proteins, which consists of six members that are involved in many vital biological functions. However, the regulation of lung fibroblasts mediated by CCN6 protein has not been fully elucidated. Here, we demonstrated that CCN6 induced the proliferation of lung fibroblasts by binding to integrin β1, leading to the phosphorylation of FAKY397. Furthermore, CCN6 showed a weak, but significant, ability to stimulate the expression of fibronectin. CCN6 was highly expressed in the lung tissues of mice treated with bleomycin. Our results suggest that CCN6 plays a role in the fibrogenesis of the lungs mainly by stimulating the growth of lung fibroblasts and is a potential target for the treatment of pulmonary fibrosis. J. Med. Invest. 58: 188-196, August, 2011