Published August 22, 2016 - More info
Progressive tissue fibrosis is a major cause of the morbidity and mortality associated with repeated epithelial injuries and accumulation of myofibroblasts. Successful treatment options are limited by an incomplete understanding of the molecular mechanisms that regulate myofibroblast accumulation. Here, we employed in vivo lineage tracing and real-time gene expression transgenic reporting methods to analyze the early embryonic transcription factor T-box gene 4 (TBX4), and determined that TBX4-lineage mesenchymal progenitors are the predominant source of myofibroblasts in injured adult lung. In a murine model, ablation of TBX4-expressing cells or disruption of TBX4 signaling attenuated lung fibrosis after bleomycin-induced injury. Furthermore, TBX4 regulated hyaluronan synthase 2 production to enable fibroblast invasion of matrix both in murine models and in fibroblasts from patients with severe pulmonary fibrosis. These data identify TBX4 as a mesenchymal transcription factor that drives accumulation of myofibroblasts and the development of lung fibrosis. Targeting TBX4 and downstream factors that regulate fibroblast invasiveness could lead to therapeutic approaches in lung fibrosis.
Ting Xie, Jiurong Liang, Ningshan Liu, Caijuan Huan, Yanli Zhang, Weijia Liu, Maya Kumar, Rui Xiao, Jeanine D’Armiento, Daniel Metzger, Pierre Chambon, Virginia E. Papaioannou, Barry R. Stripp, Dianhua Jiang, Paul W. Noble
Original citation: J Clin Invest. 2016;126(8):3063–3079. doi:10.1172/JCI85328.
Citation for this corrigendum: J Clin Invest. 2016;126(9):3626. doi:10.1172/JCI89968.
The tamoxifen doses in the original publication were incorrect. The online version of the article has been updated with the correct doses, which are given below:
Figure 4 legend, 0.2 mg/g/dose and 0.1 mg/g/dose
Figure 5 legend, 0.2 mg/g/dose
Figure 7 legend, 0.2 mg/g/injection
Figure 8 legend, 0.2 mg/g/injection
Figure 9 legend, 0.2 mg/g/injection
Methods, second paragraph, 0.1 mg/g and 0.2 mg/g
Supplemental Figure 13, 0.2 mg/g
The authors regret the errors.