Interference with connective tissue growth factor attenuated fibroblast-to-myofibroblast transition and pulmonary fibrosis.

Abstract

BackgroundThe aberrant activation and phenotype shift of resident fibroblasts in lung tissues via fibroblast-to-myofibroblast transition (FMT) is considered a pivotal step in pulmonary fibrogenesis, resulting in excessive extracellular matrix (ECM) production and deposition. However, the molecular mechanisms regulating FMT and lung fibrosis are still unclear. Connective tissue growth factor (CTGF) has been reported to be both an ECM protein and a versatile signaling molecule that is involved in multiple pathophysiological contexts, especially fibrosis. The relationship between CTGF, FMT, and lung fibrosis has not yet been well defined.MethodsIn this study, a pulmonary fibrosis (PF) rat model and FMT cell model induced by paraquat (PQ) were established to explore the relevant regulatory mechanisms in vivo and in vitro.ResultsThe results showed that the CTGF was highly activated and was a mediator of canonical Wnt signaling during FMT and PF. The inhibition of the CTGF by small-interfering ribonucleic acid decreased the expression of FMT markers, including α-smooth muscle actin, vimentin, and collagen I, inhibited the activated Wnt signaling pathway, and ameliorated lung fibrosis.ConclusionsOur findings showed that CTGF was the key effector of the FMT and fibrotic changes, and emphasized the therapeutic potential of the inhibitor or monoclonal antibody against CTGF for PF.