title: CCN6 as a profibrotic mediator that stimulates the proliferation of lung fibroblasts via the integrin β1/focal adhesion kinase pathway.
abstract: 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 FAK(Y397). 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.
authors.affiliation: Department of Respiratory Medicine and Rheumatology, University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Rentsenkhand
authors.initials: R
authors.lastname: Batmunkh
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Nishioka
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Aono
authors.forename: Momoyo
authors.initials: M
authors.lastname: Azuma
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Kinoshita
authors.forename: Jun
authors.initials: J
authors.lastname: Kishi
authors.forename: Hideki
authors.initials: H
authors.lastname: Makino
authors.forename: Masami
authors.initials: M
authors.lastname: Kishi
authors.forename: Akio
authors.initials: A
authors.lastname: Takezaki
authors.forename: Saburo
authors.initials: S
authors.lastname: Sone
mesh_terms: D000818:Animals; D055511:CCN Intercellular Signaling Proteins / Q000502:physiology*; D049109:Cell Proliferation; D016326:Extracellular Matrix Proteins / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000502:physiology*; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology*; D008168:Lung / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000209:etiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D055511:CCN Intercellular Signaling Proteins; C400081:CCN6 protein, human; C568642:CCN6 protein, mouse; D016326:Extracellular Matrix Proteins; D019012:Integrin beta1; D051416:Focal Adhesion Protein-Tyrosine Kinases