Stearoyl-CoA desaturase 1 mitigates the progression of mouse idiopathic pulmonary fibrosis in mice by inhibiting ferroptosis of pulmonary epithelial cells
Objective To determine the role and mechanism of stearoyl-CoA desaturase 1(SCD1)in idiopathic pulmonary fibrosis(IPF)with gene knockout mice and cell lines.Methods SCD1 conditional knockout mice and BEAS-2B cells were used to compare the histological changes and ferroptosis alteration after SCD1 knockout or knockdown.The effect of the PPARα agonist Fenofibrate on SCD1 expression and its impact on IPF were also examined.Results The knockout of SCD1 worsened IPF,upregulated the levels of fibrosis-related proteins,and decreased GPX4 expression.The knockdown of SCD1 increased the lipid oxidation levels,promoted ferroptosis of epithelial cells in the lung,while Fenofibrate upregulated SCD1 expression,reduced the cellular ferroptosis,and ameliorated the severity of IPF.Conclusion SCD1 inhibition promotes the ferroptosis of epithelial cells in the lung,exacerbating IPF,while Fenofibrate can be used to treat IPF by upregulating the SCD1 expression.This study provides potential targets and candidate drugs for the prevention and control of IPF.
NETL
NSTL
万方数据
