CREPT is required for pulmonary fibrosis induced by bleomycin

Abstract Background Pulmonary fibrosis is a chronic and progressive disease that originates from interstitial lung diseases and ultimately exhibits respiratory failure in patients. The disease is characterized by focal accumulation and excessive production of extracellular matrix (ECM) from over-activated fibroblasts in the lung. Although many extrinsic factors have been identified to boost fibroblast proliferation and activation, it remains unclear how fibrosis is regulated by intrinsic factors. Methods Pulmonary fibrosis mouse model was induced by intratracheal injection of bleomycin (BLM) into CREPTWT and CREPTKO mice. In vitro study, the proliferation of mouse lung fibroblasts (MLFs) was assessed using CCK-8 assays and expression of fibrotic protein was examined following transforming growth factor (TGF)-β stimulation in MLFs. Results In this study, we found that deletion of CREPT alleviated BLM induced pulmonary fibrosis. Deletion of CREPT resulted in attenuated murine lung fibroblast proliferation, TGF-β-induced fibroblast-to-myofibroblast activation, and ECM deposition. Consistently, deletion of CREPT decreased the expression of fibrotic marker genes such as a-SMA, Col1a1, and FN1 but had no influence on the inflammation response upon the BLM challenge. Conclusions In summary, we report that CREPT is required for BLM induced pulmonary fibrosis in mice. Our study unravels an intrinsic molecular mechanism for the development of pulmonary fibrosis and provides a new target for the therapy of the interstitial lung disease.