Hesperidin alleviates pulmonary fibrosis by regulating EI24-mediated autophagy

Background: Etoposide-induced protein 2.4 (EI24), an essential component of Autophagy, is lowly expressed in pulmonary fibrosis. Hesperidin (Hes), a flavonoid, can regulate Autophagy in various diseases. However, whether Hes can inhibit pulmonary fibrosis by mechanically regulating EI24-mediated Autophagy has not been uncovered.

Methods: RLE-6TN cells were treated with transforming growth factor β1 (TGF-β1) and rats were injected with bleomycin (BLM) to construct the pulmonary fibrosis model. The effect of Hes on pulmonary fibrosis was evaluated by cell counting kit-8, immunofluorescence, hematoxylin and eosin, masson trichome staining and western blotting.

Results: Hes reduced cell viability of TGF-β1-induced RLE-6TN cells. Administration of Hes restored the decrease in Autophagy marker levels in TGF-β1-induced RLE-6TN cells. Hes inhibited the transcriptional and translational levels of α-SMA, Collagen I and fibronectin that were increased by TGF-β1 in RLE-6TN cells. Mechanically, Hes restored EI24 expression, and EI24 knockdown reversed the effect of Hes on the expressions of Autophagy and fibrosis-related proteins. Additionally, Hes enhanced Autophagy and fibrosis markers, which were worsened by EI24 knockdown in BLM-induced rats.

Conclusion: Hes activated Autophagy by upregulating EI24, which improved pulmonary fibrosis both in vitro and in vivo.

EI24; Pulmonary fibrosis; autophagy; bleomycin; hesperidin.