CCN6 as a profibrotic mediator that stimulates the proliferation of lung fibroblasts via the integrin 1/focal adhesion kinase pathway

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Idiopathic pulmonary fibrosis is a progressive and lethal disease of the lungthat is characterized by the proliferation of fibroblasts and increased deposition of theextracellular matrix. The CCN6/WISP-3 is a member of the CCN family of matricellularproteins, 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 beenfully elucidated. Here, we demonstrated that CCN6 induced the proliferation of lung fibroblastsby 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 bystimulating the growth of lung fibroblasts and is a potential target for the treatment ofpulmonary fibrosis.