Journal Article

TAZ contributes to pulmonary fibrosis by activating profibrotic functions of lung fibroblasts

Matsuzaki, Hirotaka, Mitani, Akihisa, Mikami, Yu, Yamauchi, Yasuhiro, Terasaki, Yasuhiro, Horie, Masafumi, Nagase, Takahide, Saito, Akira, Miyashita, Naoya, Jo, Taisuke, Makita, Kosuke, Urushiyama, Hirokazu, Noguchi, Satoshi, Takeshima, Hideyuki

2017

Overview

Transcriptional coactivator with PDZ-binding motif (TAZ) regulates a variety of biological processes. Nuclear translocation and activation of TAZ are regulated by multiple mechanisms, including actin cytoskeleton and mechanical forces. TAZ is involved in lung alveolarization during lung development and Taz -heterozygous mice are resistant to bleomycin-induced lung fibrosis. In this study, we explored the roles of TAZ in the pathogenesis of idiopathic pulmonary fibrosis (IPF) through histological analyses of human lung tissues and cell culture experiments. TAZ was highly expressed in the fibroblastic foci of lungs from patients with IPF. TAZ controlled myofibroblast marker expression, proliferation, migration, and matrix contraction in cultured lung fibroblasts. Importantly, actin stress fibers and nuclear accumulation of TAZ were more evident when cultured on a stiff matrix, suggesting a feedback mechanism to accelerate fibrotic responses. Gene expression profiling revealed TAZ-mediated regulation of connective tissue growth factor (CTGF) and type I collagen. Clinical relevance of TAZ-regulated gene signature was further assessed using publicly available transcriptome data. These findings suggest that TAZ is involved in the pathogenesis of IPF through multifaceted effects on lung fibroblasts.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/89 / 38/91 / 631/80/304 / 692/699/1785 / Actin / Biomarkers / Bleomycin / Cell culture / Cell Line / Cell Movement / Cell Proliferation / Cells, Cultured / Collagen (type I) / Connective tissue growth factor / Contraction / Cytoskeleton / Feedback / Fibers / Fibroblasts / Fibroblasts - metabolism / Fibrosis / Gene Expression / Gene Expression Profiling / Gene Expression Regulation / Humanities and Social Sciences / Humans / Idiopathic Pulmonary Fibrosis - etiology / Idiopathic Pulmonary Fibrosis - metabolism / Idiopathic Pulmonary Fibrosis - pathology / Immunohistochemistry / Lung diseases / multidisciplinary / Myofibroblasts - metabolism / Nuclear transport / Pathogenesis / Phenotype / Pulmonary fibrosis / Pulmonary Fibrosis - etiology / Pulmonary Fibrosis - metabolism / Pulmonary Fibrosis - pathology / Rodents / Science / Transcription / Transcription Factors - genetics / Transcription Factors - metabolism / Translocation