Taken together, these results depict a positive-feedback loop TGFβ1-RCN3-TGFBR1 as a critical mechanism in the pathogenesis of pulmonary fibrosis (shown as a schematic illustration in Fig. 8): upon injury-repair activation, TGFβ1 stimulation enhances RCN3 expression in interstitial lung fibroblast and such induction of RCN3 releases the EZH2/H3K27me3-dependent repression of TGFBR1 via RCN3-EZH2 interaction, leading to enhanced TGFBR1 expression and then persistent activation of TGFβ1 signalling. Here, TGFBR1 is linked to pulmonary fibrosis.